Treatment of liver injury

ABSTRACT

A method of treating an injury in an organ or tissue includes administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes involved in the regeneration and functional compensation of the tissue or organ in response to the injury.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Applications Nos. 62/925,693, filed Oct. 24, 2019, and 62/807,569, filed Feb. 19, 2019. The entire contents of the above-identified applications are hereby fully incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under Grant Nos. GM119419 HG0061931, DA046277, DK111151, DK090311, DK105198, OD017870 awarded by the National Institutes of Health. The government has certain rights in the invention.

TECHNICAL FIELD

The subject matter disclosed herein is generally directed to treating injuries in organs and tissues.

BACKGROUND

The liver is a vital organ with a wide array of functions, including homeostasis of glucose, protein, and lipid metabolism, production of bile, synthesis of critical serum proteins, and metabolism of endogenous and xenobiotic toxins and toxicants. Because of its essential role in detoxification, the liver experiences frequent toxic insults leading to injury, cell death, and loss of functional cell mass. However, the liver has an unparalleled capacity to regenerate in order to maintain function. Under extreme stress, the regenerative capacity of the liver can be overwhelmed, leading to acute liver failure (ALF) and, ultimately, death.

SUMMARY

In certain example embodiments, methods of treating liver injury are provided comprising stimulating functional compensation in liver cells by administering an agent that stimulates macrophage Wnt signaling. In an aspect, administering an agent comprises delivering a vector that targets liver macrophages, or comprises delivery of an agent targeting hepatocytes thereby stimulating macrophage Wnt signaling at the site of livery injury.

Methods of decreasing cancer susceptibility and/or inflammation are also provided comprising administering a subject in need thereof an inhibitor of peroxisome proliferator-activated receptors (PPARs), which may comprise a alpha, beta/delta or gamma PPAR.

In embodiments administration of the inhibitor is localized to the gut or localized to the liver. In an aspect, the subject treated is obese or on a high fat diet.

Methods of reducing risk of proliferation disorders or cancer in the liver comprising administering to a subject in need thereof an agent that increases expression of Sox9 or decreases expression of Lrg5 and Axin 2.

The present disclosure provides for methods and compositions for treating injuries in organs or tissues. In one aspect, the present disclosure provides a method of treating an injury in an organ or tissue, comprising administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes or gene products that have functions in regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof.

In some embodiments, the method further comprises administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in PPAR signaling pathway, complement and/or coagulation cascades, PPARa activated gene expression, biological oxidations, metabolism of lipids and lipoproteins, nasopharyngeal carcinoma, intestine probiotics, plasma cell vs plasmablast, liver cancer, liver specific genes, multiple myeloma, response to UVb radiation, heart atrium vs ventricle, aging kidney no blood, endocrine therapy resistance, liver cancer, breast cancer basal, foxa2 targets, stem cell, lung cancer kras, tlx targets, liver cancer subclass g123, liver cancer subclass proliferation, liver cancer stem cell, liver cancer recurrence, liver cancer subclass s3, hepatoblastoma, liver development, liver hnf1a targets, matrisome, liver cancer krt19, fatty acid catabolic process, ammonium ion metabolic process, protein activation cascade, regulation of wound healing, response to estradiol, response to acid chemical, sterol homeostasis, lipoprotein metabolic process, fatty acid beta oxidation, protein maturation, regulation of locomotion, organic hydroxy compound metabolic process, organic acid biosynthetic process, monocarboxylic acid metabolic process, response to inorganic substance, regulation of vesicle mediated transport, regulation of fatty acid metabolic process, organic hydroxy compound transport, defense response, organophosphate ester transport, lipid homeostasis, secretion, anion transport, regulation of lipid biosynthetic process, response to xenobiotic stimulus, regulation of response to external stimulus, small molecule biosynthetic process, regulation of response to external stimulus, regulation of lipid metabolic process, amine metabolic process, autophagy, regulation of secretion, apoptotic signaling pathway, acute inflammatory response, regulation of catabolic process, maintenance of location, regulation of protein secretion, organic acid metabolic process, response to oxygen levels, regulation of cellular ketone metabolic process, organic acid catabolic process, regulation of response to wounding, regulation of extrinsic apoptotic signaling pathway, cellular lipid catabolic process, regulation of reactive oxygen species metabolic process, detoxification, regulation of peptidase activity, organic anion transport, inflammatory response, negative regulation of cell death, fatty acid metabolic process, lipid metabolic process, divalent inorganic cation homeostasis, regulation of endocytosis, alcohol metabolic process, immune response, cellular lipid metabolic process, monocarboxylic acid transport, negative regulation of apoptotic signaling pathway, multicellular organismal homeostasis, organic hydroxy compound biosynthetic process, regulation of cell death, lipid catabolic process, regulation of lipid metabolic process, regulation of steroid metabolic process, regulation of inflammatory response, response to toxic substance, cellular chemical homeostasis, regulation of transport, regulation of lipid catabolic process, regulation of immune effector process, lipid localization, regulation of proteolysis, regulation of secretion, regulation of response to wounding, regulation of multicellular organismal process, cellular homeostasis, single organism catabolic process, response to oxidative stress, behavior, acute phase response, regulation of response to external stimulus, regulation of apoptotic signaling pathway, regulation of cell proliferation, response to reactive oxygen species, endocytic vesicle, endoplasmic reticulum part, endoplasmic reticulum lumen, endoplasmic reticulum, lipid transporter activity, sulfur compound binding, steroid binding, glycosaminoglycan binding, alcohol binding, carboxylic ester hydrolase activity, lipid binding, receptor binding, coenzyme binding, adipogenesis, xenobiotic metabolism, fatty acid metabolism, coagulation, bile acid metabolism, peroxisome, or a combination thereof.

In some embodiments, the method further comprises administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in HDAC3 targets, photodynamic therapy stress, CEBP targets, tolerant macrophage, response to salirasib, adult tissue stem module, klfl targets, anatomical structure formation involved in morphogenesis, circulatory system process, cellular response to external stimulus, response to wounding, cellular response to extracellular stimulus, cell activation, cellular response to oxygen containing compound, vesicle mediated transport, enzyme linked receptor protein signaling pathway, response to bacterium, regulation of catabolic process, response to ketone, regulation of cell adhesion, response to hormone, blood vessel morphogenesis, response to estrogen, response to radiation, response to extracellular stimulus, cellular response to nitrogen compound, regulation of catalytic activity, vasculature development, response to abiotic stimulus, response to drug, response to growth factor, regulation of protein metabolic process, transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to peptide, hexose metabolic process, cellular response to stress, endocytosis, circulatory system development, response to starvation, hemostasis, response to molecule of bacterial origin, cell surface, peptidase regulator activity, molecular function regulator, peptidase inhibitor activity, phospholipid binding, TNF-a signaling via NFkB, or a combination thereof.

In some embodiments, the agent modulates expression and/or activity of one or more genes or gene products in Wnt pathway. In some embodiments, the agent modulates expression and/or activity of one or more genes or gene products that are markers of hepatic stem cells. In some embodiments, the expression and/or activity of the one or more genes or gene products is altered both in response to a zone-dependent injury and a zone-independent injury.

In some embodiments, the one or more genes or gene products comprises Gclc, Txnrd1, Lars2, Cyp4a14, Apoc2, Apoc1, Cyp2c29, Mt1, Mt2, Saa1, Saa2, Fgl1, Mup17, Mup18, Mup11, Gm23935, mmu-mir-6236, Ly6e, Rnase4, Saa4, Fgl1, Hp, Hpx, Lcn2, Orm1, Apcs, Orm2, Saa1, Saa2, Saa3, Sds, Tacc2, Igfbp1, Cxc11, Thrsp, Serpina3n, Lpin1, Steap4, Mt1, Mt2, Aldh3a2, Cyp2c37, Cyp2c29, Cyp8b1, Ces1d, Apoc1, Hsd17b13, Atp5h, Apoc2, Retsat, Mat1a, Angptl3, Chchd10, Hmgcs2, Cyp4a10, Cyp4a14, Gm26917, Lars2, Hyou1, Arrdc3, Mup12, Gm15564, Pdia3, Gm26924, Sephs2, Grip2, Krt8, Krt18, Plin2, Chka, Gclc, Srxn1, Hmox1, S100a8, S100a9, Mup15, Mup4, Ankrd55, Mup11, Mup5, Mup18, Mup9, Mup6, Mup17, Mup19, Alb, Pck1, Slc2a2, F2, Cyp2e1, Glu1, Arg1, Cdh1, Gls2, Ppargc1a, Sox9, Tbx3, Lgr5, Axin2, or a combination thereof.

In some embodiments, the one or more genes or gene products are selected from the genes or gene products in any one of Tables 1-8 or in all of Tables 1-8. In some embodiments, the agent induces regeneration and/or functional compensation of the organ or tissue. In some embodiments, the agent induces generation of cells that compensate function loss caused by the injury in the organ or tissue. In some embodiments, the agent induces cell proliferation in the organ or tissue. In some embodiments, the organ or tissue is liver, spleen, intestine, colon, bone marrow, an immune tissue or organ, or a tissue or organ of the gastrointestinal tract.

In some embodiments, the injury is an acute injury. In some embodiments, the injury is a chronic injury. In some embodiments, the injury is caused by a metabolic or toxic insult. In some embodiments, the injury is caused by high fat diet. In some embodiments, the injury is caused by a disease. In some embodiments, the injury is caused by a chronic disease. In some embodiments, the disease is a liver disease. In some embodiments, the liver disease is non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or cirrhosis. In some embodiments, the injury is a zone-independent injury. In some embodiments, the injury is a zone-dependent injury.

In another aspect, the present disclosure provides for a method of treating an injury in an organ or tissue, comprising determining expression of one or more genes from single cells in the organ or tissue at a first time point and a second time point; selecting a first subset of genes from the one or more genes, wherein expression of the first subset of genes at the first and the second time points are different; determining spatial locations of cells expressing the first subset of genes in the organ or tissue at the first and the second time points by an in situ hybridization assay; selecting a second subset of genes based on the spatial locations of the cells expressing the second subset of genes; and administering an agent that modulates expression and/or activity of one or more of the second subset of genes to a subject in need thereof.

These and other aspects, objects, features, and advantages of the example embodiments will become apparent to those having ordinary skill in the art upon consideration of the following detailed description of illustrated example embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

An understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention may be utilized and the accompanying drawings of which:

FIG. 1A is an overview of an exemplary approach utilized for analysis. Briefly, massively-parallel single-cell RNA-sequencing (scRNA-seq) was performed on thousands of hepatocytes, before, during and after the proliferative phase, to assess changes in the transcriptional profile of the liver following zone-dependent (APAP) compared to zone-independent (PH) injury. To add spatial context and validation of the scRNA-seq, results were coupled with single molecule fluorescence in situ hybridization (smFISH) to measure and quantify the mRNA content of hepatocytes within the mouse liver. FIG. 1B includes the time course used in the analysis to assess the transcriptional environment during injury, recovery, and termination phases of liver regeneration.

FIG. 2A dimensional reduction technique, t-Stochastic Neighbour Embedding (t-SNE), to dataset reveals a diverse population of cells. Dataset subset of hepatocytes only for further analysis, which revealed distinct separation by condition. Each UT animal is distinct; injury samples cluster together by time point with 2-3 mice per condition. Clustering by SNN outlined in black. FIG. 2B Variation in pericentral hepatocyte (PCH) and periportal hepatocyte (PPH) signature, utilizing module scores for pericentral hepatocyte (PCH) and periportal hepatocyte (PPH) gene lists over the full dataset; there is clear pericentral to periportal gradients across all clusters except 6 hours post-APAP, due to the pericentral-specific injury in this model. PC1 captures technical variation (nGene, nUMI), PC2 partly captures PCH-PPH variation, creation of module score using PCH genes. Loss of PCH in APAP6 hr (A6) of FIG. 2B due to APAP toxicity. FIG. 2C heat map of untreated versus differential expression at each timepoint following injury. FIG. 2D Venn diagram of genes up-regulated following injury and down-regulated following injury in APAP and PH.

FIG. 3A representative plot of liver lobule for genes Cyp2e1 and Glu1 at different time points and for untreated cells. FIG. 3B tSNE of PCH2 and PPH2 with APAP 6 hour clusters circled. FIG. 3C Cyp2e1 and Glu1 expression smFISH shows extension of Cyp2e1 and Glu1 expression further into midlayer than WT. smFISH analysis confirms the loss of the Cyp2e1-positive cell population directly surrounding the central vein in the APAP model at 6 and 24 hrs following exposure. combinatorial analysis of smFISH using an algorithm to define cellular outlines (CellProfiler) and counting transcripts (FISH-quant) to analyze the large number of genes that span many liver functions. FISH-quant to convert spot counts from every cell outline defined by CellProfiler into a representative heat map of the liver lobule for a given gene. Interestingly, the Cyp2e1-positive area spans an increased number of cells at 24 and 48 hrs post-APAP. Functional compensation for loss of PCH due to APAP toxicity. Compensation in Cyp2e1 and Glu1 in midlayer in APAP and PH, with functional compensation due to loss of total liver mass in PH an even greater magnitude of compensation due to later loss of tissue in PH than APAP. Evaluation includes the number of transcripts/area from a defined reference point, (central vein).

FIG. 4 —functional compensatory response can be seen in heat map and combinatorial analysis as described in FIG. 3A for other classic hepatic marker genes, including thioredoxin (Txnrd1), Albumin, gluconeogenesis gene Pck1, and the coagulation factor F2, and Gclc, a rate limiting enzyme in the synthesis of the anti-oxidant glutathione.

FIG. 5 —Pathway activation for APA 6 hour, APAP 24 hr, APAP 48/96 hr, PH 3 hr, PH48 hr and PH 120 hr·g the ability to proliferate or if these are mutually exclusive events.

FIG. 6A—Exploration of the scRNA-seq data set provides cell cycling data scores at indicated time points. FIG. 6B percent cycling cells per sample at different time points post-injury and for UT cells. FIG. 6C shows cycling cells express hepatocyte functional genes at a lower level, Left panel: hepatocyte score vs. cell cycle score, Right panel: PC-PP Score vs. Cell Cycle Score shows no strong PP=PC preference in cycling cells. FIG. 6D PCNA/smFISH staining indicates cells upregulating Glu1 are largely PCNA negative, with proliferating and compensating cells appearing to be distinct populations. FIG. 6E includes imaging showing Glutamate Synthetase (Glu1), Proliferating Cells (PCNA), and Composite image of UT cells and treated cells at APAP 24 hr, APAP 48 hr, PH 3 hr, and PH 48 hr.

FIG. 7A—plots of Cyp2f2, Cyp2e1, Alb and Hepatocyte Sig1 at APAP 24 hour and PH 48 hr. FIG. 7B heatmap PH 48 hours. FIG. 7C heatmap APAP at 24 hours.

FIG. 8A—Wnt violin plot of UT and times APAP6, APAP24, APAP48, APAP96, PHX3, PHX48, PHX120. FIG. 8B Wnt Signaling Pathway activation score at each times A6, A24, A48, A96, PHX3, PHX48, and PHX120. FIG. 8C overview of partial hepatectomy study in wild type mice, B-cat knockout, and Wt1s knockout mice, and RNA/area of each mouse for Alb and Mt1baseline and at 24 hours.

FIG. 9A—liver zonation across the lobule, with accomplishment of its many functions through division of labor. FIG. 9B—zone-dependent injury model by acetaminophen (APAP) acute toxicity in the liver. FIG. 9C—H&E, TUNEL and FISHCyp2e1 imaging of APAP zone-dependent injury model.

FIG. 10 —heatmap of marker genes per cluster injury response genes include APAP metabolism, Redox, Liver function, Tissue damage. UT up-reg genes mainly Mup (pheromone-related). Key: Gclc=Glutathione synthesis rate limiting step; Txnrd1=redox; Lars2=protein syth; Cyp=Cytochrome P450; Apo=lipid metabolism; Mt=redox, ion scavenging for proliferation; Saa=response to inflammation/tissue injury; Fgl1=Fibrinogen/clotting factor; Mup=major urinary protein/pheromone-related.

FIG. 11A—Return of Pericentral Hepatocytes (PCHs) at APAP 24 hr. Peak proliferative window known to occur 30-36 hours, PCH gene expression returns at APAP 24 hr. See cycling cells at 24 in RNA data in FIG. 6A-6E, not until 48 hr in PCNA staining CDKN1A (Cyclin Dependent Kinase Inhibitor 1A) (aka P21) is up in pre-proliferative time points. FIG. 11B depicts approach smFISH to explore spatial distribution of PCH gene expression across liver lobule, Profile pericentral-specific genes: Cyp2e1—responsible for APAP toxicity, Glu1—Highly restricted to PC region, correlated with Cyp2e1.

FIG. 12 —Heatmap shows similar functional compensation in APAP and PH with up-regulation of genes and expression beyond typical PC boundary in both injury models with some shared response genes evident in top markers for each condition. Key: Gclc=Glutathione synthesis rate limiting step; Txnrd1=redox; Lars2=protein syth; Cyp=Cytochrome P450; Apo=lipid metabolism; Mt=redox, ion scavenging for proliferation; Saa=response to inflammation/tissue injury; Fgl1=Fibrinogen/clotting factor; Mup=major urinary protein/pheromone-related.

FIG. 13 —charts of shared and unique pathways between APAP and PH treatment. See also Tables 9-11.

FIG. 14 —smFISH confirms compensation for APAP specific genes include Txnrd response to ROS, Gclc=upregulation of glutathione production, which is consumed in APAP metabolism, smFISH confirms up-regulation of selected genes unique to APAP, with upregulation observed across the lobule.

FIG. 15 —smFISH confirms compensation for shared genes, including upregulation of Mt1, Alb, F2 and Pck1 observed across the lobule in both APAP and PH injury.

FIG. 16 —PCNA/smFISH staining of Glu1 shows cells upregulating Glu1 are largely PCNA negative; proliferating cells appear to be distinct from compensating cells.

FIG. 17A depiction of extension of current studies to other organs and from acute injury to chronic injury. FIG. 17B high fat diets can lead to liver and intestinal inflammation and cancer; liver stages as a result of high fat diet include Non Alcoholic Fatty Liver disease (NALFD)=fat accumulation; NASH (non-alcoholic steatohepatitis)=steatohepatitis, fat+inflammation+scarring; Cirrhosis=scar tissue replacing liver cells. FIG. 17C—schematic of protocol for biological expansion of studies utilizing high fat diet to study multiple organs including liver and intestines with subsequent sorting of cells, peripheral blood, and spleen and bone marrow (pilot only).

FIG. 18A-18G Hepatocytes respond to toxic and surgical liver injuries. FIG. 18A Time course depicting analysis time points during liver injury recovery following APAP overdose or PH. FIG. 18B Murine liver sections (5 μm, n=3) show necrotic TUNEL-positive (top) and proliferative PCNA-positive (bottom) cells. FIG. 18C Bar graphs quantifying total TUNEL- and PCNA-positive area. Error bars are s.e.m., P<0.05 (*) and <0.0001(****) calculated using Welch's ANOVA. FIG. 18D t-SNE plot of all high-quality hepatocytes (Methods) in the scRNA-Seq data set. Cells are colored by injury mode and time point. SNN clusters outlined in black. FIG. 18E Heatmap of marker genes for all clusters outlined in FIG. 18D. FIG. 18F, 18G Pericentral Hepatocyte Signature Score (PCH Signature Score) (left). Violin plot of normalized expression of Cyp2e1 (middle) and Glu1 (right); percent positive calculated as percentage of total cells in each condition above average normalized genes expression (dashed line). Untreated (UT) and each post-treatment are plotted for FIG. 18F APAP and FIG. 18G PH.

FIG. 19A-19E Functional compensation of hepatocytes following acute liver injury. FIG. 19A Schematic for staining and image quantification. FIG. 19B, 19C Images of liver section showing pericentral markers Cyp2e1 and Glu1 for untreated and each APAP-treated (FIG. 19B) or PH-treated (FIG. 19C) time point (left column). Cell outlined and colored by number of Cyp2e1 transcripts (dark gray, low; light gray, high) for each condition (middle column). Cell outlined and colored by number of Glu1 transcripts (black, low; light gray, high) for each condition (right column). FIG. 19D, 19E Quantification of gene expression intensity (y-axis) across the lobule (x-axis) for Cyp2e1 and Glu1. 90% of area under the curve (AUC) for UT is to the left dashed line. Total AUC posted above each plot. FIG. 19D APAP treated and FIG. 19E PH-treated.

FIG. 20A-20E. Shared and unique gene expression responses in acute livery injury models. FIG. 20A Venn diagram showing genes significantly upregulated in response to APAP and/or PH treatment compared to untreated. FIG. 20B Venn diagram of genes downregulated.

FIG. 20C Pathways with significant overlaps with differentially expressed genes. Significant pathways unique to APAP response (left), unique to PH response (middle) and significant in both responses (right). FIG. 20D Expression of oxidative stress response genes (Txnrd1 and Gclc) significantly upregulated in APAP treatment response. smFISH quantification shown as bar plot.

FIG. 20E Expression of genes representing specific hepatic functions (Alb, Pck1, F2 and Ma) as violin plots with upregulation in both APAP and PH-response by smFISH. Error bars are s.e.m.

FIG. 21A-21G. Identification and characterization of proliferating hepatocytes. FIG. 21A Violin plot of cell cycle score across all samples. Cycling cells (CC, larger dots) are identified as having a cell cycle score two standard deviations above average (dashed line). Percentage of cycling cells in each condition listed below each violin. FIG. 21B Scatter plot of Hepatocyte Score versus Cell Cycle Score. Horizontal line represents average Hepatocyte Score calculated over all untreated cells. Vertical line represents two standard deviations above the average cell cycle score.

FIG. 21C Violin plots on Hepatocyte Score for all APAP 24 hr cycling cells (CC) and an equal number of non-cycling cells (NC) from APAP24 (top) and the same for PH48 CC and NC (bottom). FIG. 21D Heatmap of marker genes of CC and NC in APAP 24 hr (left) and PH 48 hr (right). FIG. 21E Violin plots of Alb and Slc2a2 in CC and NC. FIG. 21F Co-expression of liver function genes (Slc2a2 and Alb) and PCNA. FIG. 21G Quantification of RNA expression and PCNA intensity. Functional hepatic markers are selectively maintained in proliferating hepatocytes. Alb shows a maintenance of expression (total RNA counts) in proliferating hepatocytes (mean PCNA intensity) while Slc2a2 reveals a negative correlation. Mean PCNA intensity (IF) and total RNA counts (smFISH) are plotted for individually segmented cells from three lobular areas/condition (A24 and P48) with Loess regression (line). *, effect size by Cohen's d>0.2; **, d>0.5; ***, d>0.8.

FIG. 22A-22D. Contribution of Wnt signaling to functional compensation of hepatocytes. FIG. 22A Wnt target gene expression score over cycling cells (CC) and non-cycling cells (NC) from A24 and PH48. FIG. 22B hepatocytes grouped by treatment condition (UT, A6, and P3) FIG. 22C Wnt knockout mouse models. FIG. 22D Hepatocyte marker expression (Alb and Arg1) in untreated and PH 24 hr for wild type (WT), endothelial cell Wntless KO (EC-Wls), and macrophage Wntless KO (Mac-Wtls) by smFISH. FIG. 22E Average RNA expression of hepatocyte markers (Alb, Arg1, Cyp2e1, and Glu1) in untreated and PH 24 hr for WT, EC-Wls, and Mac-Wtls by smFISH. Error bars represent s.e.m., P<0.05 (*), <0.005 (**), <0.0005 (***), and <0.0001 (****).

FIG. 23A-23B. Model of hepatocyte response to acute liver injury. FIG. 23A Wnt secretion from the pericentral endothelium functions in the maintenance of the pericentral gene expression gradient in normal, quiescent liver. FIG. 23B Wnt secretion from macrophages aids in functional compensation of midzonal and periportal hepatocytes during the pre-proliferation phase of acute liver injury. FIG. 23C Wnt secretion is essential for both functional compensation and activation of the proliferative response during regeneration. Compensating hepatocytes contribute to a maintenance of hepatic function, whereas proliferating hepatocytes selectively down-regulate a subset of hepatic genes.

FIG. 24A-24E scRNA-Seq Data Processing. FIG. 24A log(nGene) and log(nUMI) for each treatment condition. FIG. 24B t-SNE colored by mouse of origin. FIG. 24C t-SNE colored by cluster. Clusters are numbered from most to fewest member cells and annotated by cell type. FIG. 24D Violin plots for marker gene expression and percent mitochondrial content (percent.mito) in each cluster. FIG. 24E Hepatocyte Signature Scores for cells in good quality hepatocyte clusters, grouped by treatment condition. Cells scoring less than 3 standard deviations below the mean (dashed line) were filtered out as non-hepatocytes. Remaining cells were included in the high-quality hepatocyte dataset for further analysis.

FIG. 25A-25H Hepatocyte dataset analysis. FIG. 25A Principle Components Analysis (PCA) of hepatocyte dataset, PC1, PC2. Cells (dots) colored by treatment condition. FIG. 25B Violin plot of PC1 and PC2 scores for each cell, grouped by treatment condition. FIG. 25C t-sne, shaded by mouse of origin. FIG. 25D t-SNE colored by SNN clustering assignment. FIG. 25E PCA (PC1, PC2), colored by lognUMI, lognGene, Periportal Hepatocyte (PPH) Signature, and Pericentral Hepatocyte (PCH) Signature. Dark gray, low; light gray, medium; medium gray, high.

FIG. 25F Violin plots of genes used to calculate PPH Sig and PCH Sig, grouped by treatment condition. FIG. 25G PPH Signature cs. PCH Signature FIG. 25H t-sne colored by lognGene, lognUMI, percent mitochondrial content (percent.mito) and Hepatocyte Signature Score. Dark gray, low; light gray, medium; medium gray, high.

FIG. 26A-26D Workflow for smFISH data analysis. Overview summarizing different steps to obtain spatial expression gradients from smFISH images. Additional details in the methods section. Cells were automatically segmented with CellProfiler (FIG. 26A) and individual mRNA molecules were detected with FISH-quant (FIG. 26B). FIG. 26C In each image, the central vein (C.V.) and portal vein (P.V.) were manually annotated as polygons in ImJoy. FIG. 26D The normalized expression gradients were calculated with an ImJoy plugin as follows: for each RNA the distance to the polygon of the C.V. is calculated (positive values for mRNAs outside the C.V., negative values for mRNAs inside the C.V.). These distances are renormalized with the closest distance between the polygon of the C.V. and the center of mass of the polygon defining the P.V. A normalized distance value of 0 thus corresponds to a position at the C.V., whereas a value of 1 corresponds to a position at the center of mass of the P.V. Renormalized distances are summarized in a histogram with a bin width of 0.1. Finally, this histogram is normalized to consider that not all distances are equally represented in the image, e.g., a proportionally larger region close to the C.V. is present in the image. For this, Applicant calculated the distance of all pixels in the image to the C.V. and summarized these measurements in a histogram as described for the RNA distance. Each bin of the RNA distance histogram is then divided by the corresponding bin of the latter histogram.

FIG. 27A-27D Average RNA expression of Cyp2e1 and Glu1 following acute liver injury. Average RNA expression quantified by smFISH of Cyp2e1 FIG. 27A and Glu1 FIG. 27B following injury induced by APAP or PH. FIG. 27C Imaging of liver section showing periportal marker Arg1 for untreated and each APAP-treated or PH-treated time point (left column). Cell outlined and colored by number of Arg1 transcripts (dark gray, low; light gray, high) for each condition. FIG. 27D Quantification of gene expression intensity across the lobule for Arg1.

FIG. 28A-28D Hepatocyte gene expression following acute liver injury using smFISH. Imaging of liver section (5 μm) showing spatiotemporal maps of the number of transcripts counted (dark gray, low; light gray, high) for hepatic genes corresponding to FIG. 28A secreted proteins, FIG. 28B metabolism, FIG. 28C ion homeostasis, and FIG. 28D glucose homeostasis. Quantification of gene expression intensity (y-axis) across the lobule (x-axis) for each gene can be found below each image set. Total AUC is posted above each plot.

FIG. 29A-29I—Cycling Cells Figure. FIG. 29A Barplot of percentage of hepatocytes from each treatment condition which were classified as cycling cells. FIG. 29B t-SNE of all hepatocytes classified as cycling cells (CC, orange) or non-cycling cells (NC, aqua). FIG. 29C Violin plot of hepatocyte signature score (module score calculated over a list of hepatocyte genes) grouped by treatment condition. FIG. 29D Scatter plot of Periportal-pericentral Score (positive more periportal, negative more pericentral) versus Cell Cycle Score. Horizontal line represents average Periportal-pericentral Score calculated over all untreated cells. Vertical line represents two standard deviations above the average cell cycle score. FIG. 29E Periportal-pericentral Score for cycling (CC) and non-cycling (NC) cells in A24 (top; p=2.7e-04; Cohen's d effect size=−0.85) and PH48 (lower; p=0.25; Cohen's d effect size=−0.17). FIG. 29F violin plot lognUMI and Wnt target genes FIG. 29G for cycling (CC) and non-cycling (NC) cells for A24 and PH48. FIG. 29H Violin plot of Cdkn1a expression by treatment condition. FIG. 29I Pathway analysis of differentially expressed genes between CC and NC in APAP 24 hr and PH48 hr.

FIG. 30 Expression of putative hepatic stem cell markers following acute liver injury using smFISH. Imaging of liver section (5 μm) showing spatiotemporal maps of the number of transcripts counted (dark gray, low; light gray, high) for putative hepatic stem cell markers Axing, Sox9, and Tbx3. Quantification of gene expression intensity (y-axis) across the lobule (x-axis) for each gene can be found below each image set. Total AUC is posted above each plot.

FIG. 31A-31D Expression of hepatic genes in β-catenin KO mice following PH Average RNA expression of hepatic genes Alb (FIG. 31A), Arg1 (FIG. 31B), Cyp2e1 (FIG. 31C), and Glu1 (FIG. 31D) in WT and β-catenin KO mice in control and 24 hrs after PH. Functional compensation of Alb and Glu1 appears to be dependent on β-catenin, whereas compensation of Arg1 and Cyp2e1 is independent.

FIG. 32A-32C Quantification of macrophages in Wntless KO mice. FIG. 32A Quantification of gene expression intensity across the lobule for Cyp2e1, Arg1, Glu1, and Alb for WT, EC-Wls KO, and Mac-Wls KO mice. Represented is control versus 24 hrs following PH. FIG. 32B IHC staining for macrophages (F4/80+) in WT, EC-Wls KO, and Mac-Wls KO mice in control and 24 hrs after PH. FIG. 32C Quantification of macrophages (F4/80+) in WT, EC-Wls KO, and Mac-Wls KO mice in control and 24 hrs after PH. Results represent four 40× fields per group. Error bars are indicative of s.e.m.

FIG. 33A-33E. Identification of cell types in full dataset. FIG. 33A t-SNE of all sequenced cells passing initial filter, colored by compartment of origin. FIG. 33B t-SNE of full dataset colored by diet condition, CD (gray) or HFD (dark gray). FIG. 33C t-SNEs colored by module score calculated over marker genes for expected cell types, and number of genes captured (nGene), and percent mitochondrial content (percent.mito). Dark gray, low; light gray, intermediate; gray, high. FIG. 33D t-SNE showing SNN clustering (numbered with 0 being the cluster with the most cells, to 29, the cluster with the fewest). Clusters are annotated with cell type and, for samples primarily from a particular sample, major sample type of origin. FIG. 33E Stacked barplot showing fractional abundance of cells from each mouse in each cluster. HF mice are shown in medium to dark grays, CD mice in light gray.

FIG. 34A-34D Analysis of gut-originating populations. FIG. 34A t-SNE over gut-originating samples only, shaded by gut location (colon, distal small intestine, proximal small intestinal) and diet (CD, HF). FIG. 34B t-SNE with SNN clustering, clusters numbered from most to fewest cells. Clusters are annotated with cell type and sample of origin. FIG. 34C PPAR signature score calculated for CD (light shade, left) and HF (dark shade, right) cells in each cluster. Effect size calculated by Cohen's d: d<0.2=n (negligible); 0.2<d<0.5=* (small); 0.5<d<0.8=** (medium), d>0.8=*** (large). FIG. 34D Fractional abundance of HF and CD cells for each type of immune cell in gut dataset.

FIG. 35A-35I Analysis of liver-originating populations. FIG. 35A t-SNE of liver-originating samples, colored by sample type and diet condition. FIG. 35B SNN clustering. Clusters annotated with cell type. Cells originating from control lighter colored; cells originating from HFD vibrant colored. FIG. 35C Stacked barplot of fractional abundance of cells from each mouse in each identified liver sample cluster. HFD gray; CD dark gray. FIG. 35D Iterative clustering over non-parenchymal liver cells (NPCs). SNN clustering and cell type annotation. FIG. 35E t-SNE of NPC liver cells colored by diet condition. FIG. 35F IPA functions and upstream regulators upregulated in HFD cs. CD Kupffers FIG. 35G Iterative clustering over hepatocytes. Shaded by mouse of origin. SNN clusters outlined in black. FIG. 35H PPAR activation signature score over hepatocyte clusters. FIG. 35I CEBPA activation signature score over hepatocyte clusters. Effect size calculated by Cohen's d.

FIG. 36A-36C Stem cell gene expression in hepatocytes. FIG. 36A Expression of liver stem cell genes module score in CD and HFD hepatocytes. Liver stem cells called as scoring two standard deviations above the average (dashed line). Percentage of stem cells in each sample listed below. FIG. 36B Violin plots of expression of selected genes from the stem cell module. FIG. 36C Biaxial plot of Axin2 vs Lgr5 expression in identified stem cells.

FIG. 37A-37C Hepatocyte-derived organoid growth. FIG. 37A Heptocytes seeded in matrigel at 0 days. Growth at 8 and 14 days, small, growing organoids circled in CD Day 8. FIG. 37B Organoids after 2 months in culture. FIG. 37C ATPase growth assay on organoids after 2 months in culture. ANOVA with corrections for multiple comparisons.

The figures herein are for illustrative purposes only and are not necessarily drawn to scale.

DETAILED DESCRIPTION OF THE EXAMPLE EMBODIMENTS General Definitions

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Definitions of common terms and techniques in molecular biology may be found in Molecular Cloning: A Laboratory Manual, 2^(nd) edition (1989) (Sambrook, Fritsch, and Maniatis); Molecular Cloning: A Laboratory Manual, 4^(th) edition (2012) (Green and Sambrook); Current Protocols in Molecular Biology (1987) (F. M. Ausubel et al. eds.); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (1995) (M. J. MacPherson, B. D. Hames, and G. R. Taylor eds.): Antibodies, A Laboratory Manual (1988) (Harlow and Lane, eds.): Antibodies A Laboraotry Manual, 2nd edition 2013 (E. A. Greenfield ed.); Animal Cell Culture (1987) (R.I. Freshney, ed.); Benjamin Lewin, Genes IX, published by Jones and Bartlet, 2008 (ISBN 0763752223); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0632021829); Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 9780471185710); Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992); and Marten H. Hofker and Jan van Deursen, Transgenic Mouse Methods and Protocols, 2nd edition (2011).

As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.

The term “optional” or “optionally” means that the subsequent described event, circumstance or substituent may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.

The terms “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of +/−10% or less, +1-5% or less, +/−1% or less, and +/−0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed.

As used herein, a “biological sample” may contain whole cells and/or live cells and/or cell debris. The biological sample may contain (or be derived from) a “bodily fluid”. The present invention encompasses embodiments wherein the bodily fluid is selected from amniotic fluid, aqueous humour, vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen (earwax), chyle, chyme, endolymph, perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus (including nasal drainage and phlegm), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum (skin oil), semen, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, vomit and mixtures of one or more thereof. Biological samples include cell cultures, bodily fluids, cell cultures from bodily fluids. Bodily fluids may be obtained from a mammal organism, for example, by puncture, or other collecting or sampling procedures. In certain embodiments, a biological sample may contain cells, such as preferably live cells, cell-derived vesicles, cell debris and/or extracellular fluid, such as particularly from liver, spleen, intestine, colon, bone marrow, an immune tissue or organ, or a tissue or organ of the gastrointestinal tract.

The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. The term subject is further intended to include transgenic non-human species.

Various embodiments are described hereinafter. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader aspects discussed herein. One aspect described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced with any other embodiment(s). Reference throughout this specification to “one embodiment”, “an embodiment,” “an example embodiment,” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” or “an example embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention. For example, in the appended claims, any of the claimed embodiments can be used in any combination.

All publications, published patent documents, and patent applications cited herein are hereby incorporated by reference to the same extent as though each individual publication, published patent document, or patent application was specifically and individually indicated as being incorporated by reference.

Overview

The present disclosure provides for methods of treating injury in an organ or tissue. In general, the methods include administering to a subject in need thereof an agent that induces regeneration and functional compensation of the organ or tissue. The work described herein provides a mechanism by which the liver maintains essential physiological functions prior to the onset of cellular reconstitution and characterizes macrophage-derived WNT signals required for this compensation.

Methods of Treatment

In one aspect, the present disclosure provides methods for treating an injury in an organ or tissue. In general, the methods include modulating the expression and/or activity of one or more genes. Such genes may have functions in regeneration of the organ or tissue. For examples, these genes may be involved in cell proliferation in the organ or tissues. Alternatively or additionally, these genes may have functions in functional compensation for loss of function in the organ or tissue due to the injury. For example, the genes may be involved in generating new cells or reprogramming existing cells to compensate the loss of function. In some embodiments, the methods include administering one or more agents that modulate the expression and/or activity of these genes or one or more genes of a defined pathway. The one or more agents may be administered to cells in an organ or tissue. The cells may be liver, spleen, intestine, colon, bone marrow, or an organ of the gastrointestinal tract. In certain embodiments, the cells are liver cells. The methods of treatment are to compensate or induce cell proliferation in which a tissue or organ is injured. In an aspect, the injury is an acute injury or chronic injury. The injury can be a disease, such as a metabolic disease, or can be due to surgery or toxicity exposure.

As used herein, the terms “treat”, “treating” and “treatment” refer to the alleviation or measurable lessening of one or more symptoms or measurable markers of an injury, disease or disorder. Measurable lessening includes any statistically significant decline in a measurable marker or symptom. In some embodiments, treatment is prophylactic treatment.

The treatment method may include administering a therapeutically effective amount of agent. The term “therapeutically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result, e.g., a diminishment or prevention of effects associated with various disease states or conditions. The term “therapeutically effective amount” refers to an amount of a target gene or gene product modulator effective to treat or prevent a disease or disorder in a mammal. A therapeutically effective amount of a target gene or gene product modulator can vary according to factors such as the disease state, age, sex, and weight of the subject, and the ability of the therapeutic compound to elicit a desired response in the subject. A therapeutically effective amount is also one in which any toxic or detrimental effects of the therapeutic agent are outweighed by the therapeutically beneficial effects. In some embodiments, a therapeutically effective amount is an “effective amount”, which as used herein refers to the amount of therapeutic agent of pharmaceutical composition to alleviate at least one or some of the symptoms of the disease or disorder. An “effective amount” for purposes herein is thus determined by such considerations as are known in the art and is the amount to achieve improvement including, but not limited to, improved survival rate or more rapid recovery, or improvement or elimination of at least one symptom and other indicator of an immune or autoimmune disease which are appropriate measures by those skilled in the art. It should be noted that a target gene or gene product modulator as disclosed herein can be administered as a pharmaceutically acceptable salt and can be administered alone or as an active ingredient in combination with pharmaceutically acceptable carriers, diluents, adjuvants and vehicles.

The treatment method may include administering a prophylactically effective amount of agent. The term “prophylactically effective amount” refers to an amount of a target gene or gene product modulator which is effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result, e.g., the amount of a target gene or gene product modulator. Typically, since a prophylactic dose of a target gene or gene product modulator is administered to a subject prior to or at an earlier stage of a disease, in some embodiments, a prophylactically effective amount is less than the therapeutically effective amount. A prophylactically effective amount of a target gene or gene product modulator is also one in which any toxic or detrimental effects of the compound are outweighed by the beneficial effects.

As used herein, the terms “prevent”, “preventing” and “prevention” refer to the avoidance or delay in manifestation of one or more symptoms or measurable markers of a disease or disorder. A delay in the manifestation of a symptom or marker is a delay relative to the time at which such symptom or marker manifests in a control or untreated subject with a similar likelihood or susceptibility of developing the disease or disorder. The terms “prevent,” “preventing,” and “prevention” include not only the avoidance or prevention of a symptom or marker of the disease, but also a reduced severity or degree of any one of the symptoms or markers of the disease, relative to those symptoms or markers in a control or non-treated individual with a similar likelihood or susceptibility of developing the disease or disorder, or relative to symptoms or markers likely to arise based on historical or statistical measures of populations affected by the disease or disorder.

By “reduced severity” is meant at least a 10% reduction in the severity or degree of a symptom or measurable disease marker, relative to a control or reference, e.g., at least 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% or even 100% (i.e., no symptoms or measurable markers).

As used herein, the terms “administering” and “introducing” are used interchangeably herein and refer to the placement of the agents of metabolic regulators of the present invention into a subject by a method or route which results in at least partial localization of a target gene or gene product modulator at a desired site. The compounds of the present invention can be administered by any appropriate route which results in an effective treatment in the subject. In some embodiments, administering is not systemic administration.

The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intraventricular, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, sub capsular, subarachnoid, intraspinal, intracerebro spinal, and intrasternal injection and infusion. The phrases “systemic administration”, “administered systemically”, “peripheral administration” and “administered peripherally” as used herein mean the administration of a modulator such that it enters the animal's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

Target Genes and Pathways for Treating Injuries

The expression and/or activity of one or more genes or signaling pathways may be modulated for treating injuries in organs or tissues. As used herein, the term “gene” refers to a nucleic acid comprising an open reading frame encoding a polypeptide, including both exon and (optionally) intron sequences. A “gene” refers to coding sequence of a gene product, as well as non-coding regions of the gene product, including 5′UTR and 3′UTR regions, introns and the promoter of the gene product. The coding region of a gene can be a nucleotide sequence coding for an amino acid sequence or a functional RNA, such as tRNA, rRNA, catalytic RNA, siRNA, miRNA and antisense RNA. A gene can also be an mRNA or cDNA corresponding to the coding regions (e.g. exons and miRNA) optionally comprising 5′- or 3′ untranslated sequences linked thereto. These definitions generally refer to a single-stranded molecule, but in specific embodiments will also encompass an additional strand that is partially, substantially or fully complementary to the single-stranded molecule. Thus, a nucleic acid may encompass a single-stranded molecule or a double-stranded molecule that comprises one or more complementary strand(s) or “complement(s)” of a particular sequence comprising a molecule. As used herein, a single-stranded nucleic acid may be denoted by the prefix “ss”, a double stranded nucleic acid by the prefix “ds”, and a triple stranded nucleic acid by the prefix “is”. The term “gene” may refer to the segment of DNA involved in producing a polypeptide chain, it includes regions preceding and following the coding region as well as intervening sequences (introns and non-translated sequences, e.g., 5′- and 3′-untranslated sequences and regulatory sequences) between individual coding segments (exons). A gene can also be an amplified nucleic acid molecule produced in vitro comprising all or a part of the coding region and/or 5′- or 3′-untranslated sequences linked thereto.

All gene name symbols refer to the gene as commonly known in the art. Gene symbols may be those referred to by the HUGO Gene Nomenclature Committee (HGNC). Any reference to the gene symbol is a reference made to the entire gene or variants of the gene. The HUGO Gene Nomenclature Committee is responsible for providing human gene naming guidelines and approving new, unique human gene names and symbols. All human gene names and symbols can be searched at genenames.org, the HGNC website, and the guidelines for their formation are available there (genenames.org/guidelines).

In some embodiments, the one or more genes may have functions in regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof. In some cases, the methods include further administering an additional agent to modulate one or more genes that have functions in the pathways described in this paragraph.

In some embodiments, the one or more genes may have functions in PPAR signaling pathway, complement and coagulation cascades, PPARa activated gene expression, biological oxidations, metabolism of lipids and lipoproteins, nasopharyngeal carcinoma, intestine probiotics, plasma cell vs plasmablast, liver cancer, liver specific genes, multiple myeloma, response to UVb radiation, heart atrium vs ventricle, aging kidney no blood, endocrine therapy resistance, liver cancer, breast cancer basal, foxa2 targets, stem cell, lung cancer kras, tlx targets, liver cancer subclass g123, liver cancer subclass proliferation, liver cancer stem cell, liver cancer recurrence, liver cancer subclass s3, hepatoblastoma, liver development, liver hnf1a targets, matrisome, liver cancer krt19, fatty acid catabolic process, ammonium ion metabolic process, protein activation cascade, regulation of wound healing, response to estradiol, response to acid chemical, sterol homeostasis, lipoprotein metabolic process, fatty acid beta oxidation, protein maturation, regulation of locomotion, organic hydroxy compound metabolic process, organic acid biosynthetic process, monocarboxylic acid metabolic process, response to inorganic substance, regulation of vesicle mediated transport, regulation of fatty acid metabolic process, organic hydroxy compound transport, defense response, organophosphate ester transport, lipid homeostasis, secretion, anion transport, regulation of lipid biosynthetic process, response to xenobiotic stimulus, regulation of response to external stimulus, small molecule biosynthetic process, regulation of response to external stimulus, regulation of lipid metabolic process, amine metabolic process, autophagy, regulation of secretion, apoptotic signaling pathway, acute inflammatory response, regulation of catabolic process, maintenance of location, regulation of protein secretion, organic acid metabolic process, response to oxygen levels, regulation of cellular ketone metabolic process, organic acid catabolic process, regulation of response to wounding, regulation of extrinsic apoptotic signaling pathway, cellular lipid catabolic process, regulation of reactive oxygen species metabolic process, detoxification, regulation of peptidase activity, organic anion transport, inflammatory response, negative regulation of cell death, fatty acid metabolic process, lipid metabolic process, divalent inorganic cation homeostasis, regulation of endocytosis, alcohol metabolic process, immune response, cellular lipid metabolic process, monocarboxylic acid transport, negative regulation of apoptotic signaling pathway, multicellular organismal homeostasis, organic hydroxy compound biosynthetic process, regulation of cell death, lipid catabolic process, regulation of lipid metabolic process, regulation of steroid metabolic process, regulation of inflammatory response, response to toxic substance, cellular chemical homeostasis, regulation of transport, regulation of lipid catabolic process, regulation of immune effector process, lipid localization, regulation of proteolysis, regulation of secretion, regulation of response to wounding, regulation of multicellular organismal process, cellular homeostasis, single organism catabolic process, response to oxidative stress, behavior, acute phase response, regulation of response to external stimulus, regulation of apoptotic signaling pathway, regulation of cell proliferation, response to reactive oxygen species, endocytic vesicle, endoplasmic reticulum part, endoplasmic reticulum lumen, endoplasmic reticulum, lipid transporter activity, sulfur compound binding, steroid binding, glycosaminoglycan binding, alcohol binding, carboxylic ester hydrolase activity, lipid binding, receptor binding, coenzyme binding, adipogenesis, xenobiotic metabolism, fatty acid metabolism, coagulation, bile acid metabolism, peroxisome, or a combination thereof. In some cases, the methods include further administering an additional agent to modulate one or more genes that have functions in the pathways described in this paragraph.

In some embodiments, the one or more genes may have functions in HDAC3 targets, photodynamic therapy stress, CEBP targets, tolerant macrophage, response to salirasib, adult tissue stem module, klfl targets, anatomical structure formation involved in morphogenesis, circulatory system process, cellular response to external stimulus, response to wounding, cellular response to extracellular stimulus, cell activation, cellular response to oxygen containing compound, vesicle mediated transport, enzyme linked receptor protein signaling pathway, response to bacterium, regulation of catabolic process, response to ketone, regulation of cell adhesion, response to hormone, blood vessel morphogenesis, response to estrogen, response to radiation, response to extracellular stimulus, cellular response to nitrogen compound, regulation of catalytic activity, vasculature development, response to abiotic stimulus, response to drug, response to growth factor, regulation of protein metabolic process, transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to peptide, hexose metabolic process, cellular response to stress, endocytosis, circulatory system development, response to starvation, hemostasis, response to molecule of bacterial origin, cell surface, peptidase regulator activity, molecular function regulator, peptidase inhibitor activity, phospholipid binding, TNF-a signaling via NFkB, or a combination thereof. In some cases, the methods include further administering an additional agent to modulate one or more genes that have functions in the pathways described in this paragraph.

In some examples, the one or more genes may be Gclc, Txnrd1, Lars2, Cyp4a14, Apoc2, Apoc1, Cyp2c29, Mt1, Mt2, Saa1, Saa2, Fgl1, Mup17, Mup18, Mup11, Gm23935, mmu-mir-6236, Ly6e, Rnase4, Saa4, Fgl1, Hp, Hpx, Lcn2, Orm1, Apcs, Orm2, Saa1, Saa2, Saa3, Sds, Tacc2, Igfbp1, Cxc11, Thrsp, Serpina3n, Lpin1, Steap4, Mt1, Mt2, Aldh3a2, Cyp2c37, Cyp2c29, Cyp8b1, Ces1d, Apoc1, Hsd17b13, Atp5h, Apoc2, Retsat, Mat1a, Angptl3, Chchd10, Hmgcs2, Cyp4a10, Cyp4a14, Gm26917, Lars2, Hyou1, Arrdc3, Mup12, Gm15564, Pdia3, Gm26924, Sephs2, Grip2, Krt8, Krt18, Plin2, Chka, Gclc, Srxn1, Hmox1, S100a8, S100a9, Mup15, Mup4, Ankrd55, Mup11, Mup5, Mup18, Mup9, Mup6, Mup17, Mup19, Alb, Pck1, Slc2a2, F2, Cyp2e1, Glu1, Arg1, Cdh1, Gls2, Ppargc1a, Sox9, Tbx3, Lgr5, Axin2, or a combination thereof.

In some examples, the one or more genes are selected from the genes listed in Tables 1 to 8.

The methods herein include modulating (e.g., using modulating agent(s)) one or more genes, e.g., at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 200, at least 300, at least 400, or at least 500 genes.

In some cases, the one or more genes may be in the Wnt pathway, a highly conserved signaling pathway also referred to as the Wnt/β-catenin pathway. Examples of such genes may be β-catenin, tumor suppressor gene product adenomatous polyposis coli (APC), axin, glycogen synthase kinase (GSK)-3β, TCF/LEF transcription factors (e.g. TCF4), crescent, groucho, CBP, frizzled receptor, frizzled related proteins, LRP, LRP5, LRP6, kremin, Dvl/Dsh (disheveled), dickkopf, GSK-3 binding protein (GBP), FRAT/GBP, Ebi, β-TrCP, Pin1, ICAT, E-cadherin, CKI, Lgs/BCL9, and Pygo, SFRP1, PP2A, ARFGAP1. Modulating agents and ligands of the pathway and gene products in the pathway are of particular interest. See, e.g., Shin et al., EBioMedicine 25 (2017) 22-31, incorporated by reference in its entirety.

In embodiments, the targets are Wnt that are expressed by macrophages. The macrophages may be distinct for their local environment or tissue type. Malsin et al., Fron. Immunol., 31 Jul. 2019, DOI: 10.3389/fimmu.2019.01813, incorporated herein by reference. In Malsin, et al., Table 1 identifies Wnt ligand study, role in macrophage biology, specific Wnt ligand as well as canonical or non-canonical pathway implicated, Table 1 incorporated herein specifically by reference. Wnt signaling in macrophages has included Wnt3a and Wnt5a in mycobacteria induced inflammatory responses. See, e.g. Schaale et al., DOI:10.1016/j.ejcb.2010.11.004; see also, Yang et al, Cell Death and Disease 9:793 (2018); Feng et al., JASN January 2018, 29 (1) 182-193; DOI:10.1681/ASN.2017040391, both incorporated herein by reference. In an aspect, the methods of treatment may comprise delivering a vector that can target liver macrophages specifically. In an aspect the vector can be configured to target hepatocytes such that the agent that stimulates macrophage Wnt signaling, one or more proteins or ligands of the Wnt pathway, such that the agent is released at the site of injury.

Methods of decreasing cancer susceptibility and/or inflammation are provided comprise administering a subject in need thereof an inhibitor of peroxisome proliferator-activated receptors (PPARs), alpha, gamma and delta (beta). PPARs are ligand-activated transcription factors of the nuclear hormone receptor superfamily, studied for how ligands and receptors modulate gene expression. See, e.g., Guan, The Italian Journal of Urology and Nephrology, 31 May 2002, 54(2):65-79; Rigano et al., Acta Pharm Sin B. 2017 July; 7(4): 427-438; doi: 10.1016/j.apsb.2017.05.005; Cheng et al., Mini Rev Med Chem. 2005 August; 5(8):741-53. See also, Liss et al, Biochimie. 2017 May; 136: 65-74. Doi: 10.1016/j.biochi.2016.11.009 and Souza mello, World J. Hepatol, doi: 10.4254/wjh.v7.i8.1012, both incorporated herein by reference, for discussion of PPAR receptors as targets in in Nonalcoholic fatty liver disease; and Peyrou et al, doi:10.1155/2012/757802 in liver disease and cancer, incorporated herein by reference.

A method of reducing risk of proliferation disorders or cancer in the liver comprising administering to a subject in need thereof aa modulating agent that increases expression of Sox9. Treatment with PGD2 has been shown to upregulate expression of endogenous Sox9, RAR agonists and CHX stimulation is also contemplated. See, Passeron et al, J Clin Invest. 2009 Apr. 1; 119(4): 954-963, published online 2009 Mar. 9. doi: 10.1172/JCI34015. Methods of reducing risk of proliferation disorders or cancer in the liver may also comprise administering an agent that decreases expression of Lrg5, (e.g. RNAi-mediated inhibition or other approaches, Br J Cancer. 2018 May 29; 118(11): 1410-1418, doi: 10.1038/s41416-018-0118-6, incorporated by reference) and Axin 2 (See, Gustafson et al., Front Pharmacol. 2017; 8: 285, doi: 10.3389/fphar.2017.00285; Bernkopf, D. B., Bruckner, M., Hadjihannas, M. V. et al. An aggregon in conductin/axin2 regulates Wnt/β-catenin signaling and holds potential for cancer therapy. Nat Commun 10, 4251 (2019). Doi:10.1038/s41467-019-12203-8, incorporated herein by reference). Methods of treatment increasing Sox9 and decreasing one or more of Lrg5 and Axin2 may also be utilized.

Modulating Agents

In some embodiments, the methods herein include administering one or more agents that modulate the expression and/or activity of gene(s) and/or pathway.

For example, the methods may include administering at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100 modulating agents.

As will be clear to the skilled person, “modulating” can also involve affecting a change (which can either be an increase or a decrease) in affinity, avidity, specificity and/or selectivity of a target or antigen, for one or more of its targets compared to the same conditions but without the presence of a modulating agent. Again, this can be determined in any suitable manner and/or using any suitable assay known per se, depending on the target. In particular, an action as an inhibitor/antagonist or activator/agonist can be such that an intended biological or physiological activity is increased or decreased, respectively, by at least 5%, at least 10%, at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, or 90% or more, compared to the biological or physiological activity in the same assay under the same conditions but without the presence of the inhibitor/antagonist agent or activator/agonist agent. Modulating can also involve activating the target or antigen or the mechanism or pathway in which it is involved.

“Altered expression” as intended herein may encompass modulating the activity of one or more endogenous gene products. Accordingly, “altered expression”, “altering expression”, “modulating expression”, or “detecting expression” or similar may be used interchangeably with, respectively, “altered expression or activity”, “altering expression or activity”, “modulating expression or activity”, or “detecting expression or activity” or similar. As used herein the term “altered expression” may particularly denote altered production of the recited gene products by a cell. As used herein, the term “gene product(s)” includes RNA transcribed from a gene (e.g., mRNA), or a polypeptide encoded by a gene or translated from RNA.

Modulation herein may include increasing, decreasing, abolishing, expression and/or activity of the one or more genes. The terms “increased” or “increase” or “upregulated” or “upregulate” as used herein generally mean an increase by a statically significant amount. For avoidance of doubt, “increased” means a statistically significant increase of at least 10% as compared to a reference level, including an increase of at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100% or more, including, for example at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold increase or greater as compared to a reference level, as that term is defined herein.

The term “reduced” or “reduce” or “decrease” or “decreased” or “downregulate” or “downregulated” as used herein generally means a decrease by a statistically significant amount relative to a reference. For avoidance of doubt, “reduced” means statistically significant decrease of at least 10% as compared to a reference level, for example a decrease by at least 20%, at least 30%, at least 40%, at least 50%, or least 60%, or least 70%, or least 80%, at least 90% or more, up to and including a 100% decrease (i.e., absent level as compared to a reference sample), or any decrease between 10-100% as compared to a reference level, as that term is defined herein. The term “abolish” or “abolished” may in particular refer to a decrease by 100%, i.e., absent level as compared to a reference sample.

The term “agent” as used herein generally refers to any substance or composition, such as a chemical entity or biological product, or combination of chemical entities or biological products, capable of achieving a desired effect in a system, more particularly in a biological system, e.g., in a cell, tissue, organ, or an organism. In the present context, an agent may be exposed to, contacted with or introduced into an immune cell to modify at least one characteristic of the immune cell, such as to (inducibly) alter the expression or activity of the one or more genes or gene products as taught herein by the immune cell. Further in the present context, an agent may be administered to a subject to treat or prevent or control a disease or condition, for example by (inducibly) altering the expression or activity of the one or more genes or gene products as taught herein by immune cells of the subject.

In alternative embodiments, agents useful in the methods as disclosed herein are proteins and/or peptides or fragment thereof, which inhibit the gene expression of a target gene or gene product, or the function of a target protein. Such agents include, for example, but are not limited to protein variants, mutated proteins, therapeutic proteins, truncated proteins and protein fragments. Protein agents can also be selected from a group comprising mutated proteins, genetically engineered proteins, peptides, synthetic peptides, recombinant proteins, chimeric proteins, antibodies, midibodies, minibodies, triabodies, humanized proteins, humanized antibodies, chimeric antibodies, modified proteins and fragments thereof. As disclosed herein, a protein which inhibits the function of a target protein may be a soluble dominant negative form of the target protein or a functional fragment or variant thereof which inhibits wild-type full length target protein function.

In certain embodiments, the agents may be small molecules, antibodies, therapeutic antibody, antibody fragment, antibody-like protein scaffold, aptamer, protein, genetic modifying agent or small molecule. The chemical entity or biological product is preferably, but not necessarily a low molecular weight compound, but may also be a larger compound, or any organic or inorganic molecule effective in the given situation, including modified and unmodified nucleic acids such as antisense nucleic acids, RNAi, such as siRNA or shRNA, CRISPR-Cas systems, peptides, peptidomimetics, receptors, ligands, and antibodies, aptamers, polypeptides, nucleic acid analogues or variants thereof. Examples include an oligomer of nucleic acids, amino acids, or carbohydrates including without limitation proteins, oligonucleotides, ribozymes, DNAzymes, glycoproteins, siRNAs, lipoproteins, aptamers, and modifications and combinations thereof. Agents can be selected from a group comprising chemicals; small molecules; nucleic acid sequences; nucleic acid analogues; proteins; peptides; aptamers; antibodies; or fragments thereof. A nucleic acid sequence can be RNA or DNA, can be single or double stranded, and can be selected from a group comprising nucleic acid encoding a protein of interest, oligonucleotides, nucleic acid analogues, for example, peptide-nucleic acid (PNA), pseudo-complementary PNA (pc-PNA), locked nucleic acid (LNA), modified RNA (mod-RNA), single guide RNA etc. Such nucleic acid sequences include, for example, but are not limited to, nucleic acid sequence encoding proteins, for example, that act as transcriptional repressors, antisense molecules, ribozymes, small inhibitory nucleic acid sequences, for example, but are not limited to RNAi, shRNAi, siRNA, micro RNAi (mRNAi), antisense oligonucleotides, CRISPR guide RNA, for example, that target a CRISPR enzyme to a specific DNA target sequence, etc. A protein and/or peptide or fragment thereof can be any protein of interest, for example, but are not limited to mutated proteins; therapeutic proteins and truncated proteins, wherein the protein is normally absent or expressed at lower levels in the cell. Proteins can also be selected from a group comprising mutated proteins, genetically engineered proteins, peptides, synthetic peptides, recombinant proteins, chimeric proteins, antibodies, minibodies, humanized proteins, humanized antibodies, chimeric antibodies, modified proteins and fragments thereof. Alternatively, the agent can be intracellular within the cell as a result of introduction of a nucleic acid sequence into the cell and its transcription resulting in the production of the nucleic acid and/or protein modulator of a gene within the cell. In some embodiments, the agent is any chemical, entity or moiety, including without limitation synthetic and naturally-occurring non-proteinaceous entities. In certain embodiments the agent is a small molecule having a chemical moiety. Agents can be known to have a desired activity and/or property, or can be selected from a library of diverse compounds.

In some embodiments, the one or more agents may be small molecules. The term “small molecule” refers to compounds, preferably organic compounds, with a size comparable to those organic molecules generally used in pharmaceuticals. The term excludes biological macromolecules (e.g., proteins, peptides, nucleic acids, etc.). Preferred small organic molecules range in size up to about 5000 Da, e.g., up to about 4000, preferably up to 3000 Da, more preferably up to 2000 Da, even more preferably up to about 1000 Da, e.g., up to about 900, 800, 700, 600 or up to about 500 Da.

In certain embodiments, the modulating agent can refer to a protein-binding agent that permits modulation or activity of proteins or disrupts interactions of proteins and other biomolecules, such as, but not limited to, disrupting protein-protein interaction, ligand-receptor interaction, or protein-nucleic acid interaction. Agents can also refer to DNA targeting or RNA targeting agents. Agents may include a fragment, derivative and analog of an active agent. The terms “fragment,” “derivative” and “analog” when referring to polypeptides as used herein refers to polypeptides which either retain substantially the same biological function or activity as such polypeptides. An analog includes a proprotein which can be activated by cleavage of the proprotein portion to produce an active mature polypeptide. Such agents include, but are not limited to, antibodies (“antibodies” includes antigen-binding portions of antibodies such as epitope- or antigen-binding peptides, paratopes, functional CDRs; recombinant antibodies; chimeric antibodies; humanized antibodies; nanobodies; tribodies; midibodies; or antigen-binding derivatives, analogs, variants, portions, or fragments thereof), protein-binding agents, nucleic acid molecules, small molecules, recombinant protein, peptides, aptamers, avimers and protein-binding derivatives, portions or fragments thereof.

As used herein, a “blocking” antibody or an antibody “antagonist” is one which inhibits or reduces biological activity of the antigen(s) it binds. For example, an antagonist antibody may bind a surface receptor or ligand and inhibit the ability of the receptor and ligand to induce an ILC class 2 inflammatory response. In certain embodiments, the blocking antibodies or antagonist antibodies or portions thereof described herein completely inhibit the biological activity of the antigen(s).

Antibodies may act as agonists or antagonists of the recognized polypeptides. For example, the present invention includes antibodies which disrupt receptor/ligand interactions either partially or fully. The invention features both receptor-specific antibodies and ligand-specific antibodies. The invention also features receptor-specific antibodies which do not prevent ligand binding but prevent receptor activation. Receptor activation (i.e., signaling) may be determined by techniques described herein or otherwise known in the art. For example, receptor activation can be determined by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or of one of its down-stream substrates by immunoprecipitation followed by western blot analysis. In specific embodiments, antibodies are provided that inhibit ligand activity or receptor activity by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 60%, or at least 50% of the activity in absence of the antibody.

The invention also features receptor-specific antibodies which both prevent ligand binding and receptor activation as well as antibodies that recognize the receptor-ligand complex. Likewise, encompassed by the invention are neutralizing antibodies which bind the ligand and prevent binding of the ligand to the receptor, as well as antibodies which bind the ligand, thereby preventing receptor activation, but do not prevent the ligand from binding the receptor. Further included in the invention are antibodies which activate the receptor. These antibodies may act as receptor agonists, i.e., potentiate or activate either all or a subset of the biological activities of the ligand-mediated receptor activation, for example, by inducing dimerization of the receptor. The antibodies may be specified as agonists, antagonists or inverse agonists for biological activities comprising the specific biological activities of the peptides disclosed herein. The antibody agonists and antagonists can be made using methods known in the art. See, e.g., PCT publication WO 96/40281; U.S. Pat. No. 5,811,097; Deng et al., Blood 92(6):1981-1988 (1998); Chen et al., Cancer Res. 58(16):3668-3678 (1998); Harrop et al., J. Immunol. 161(4):1786-1794 (1998); Zhu et al., Cancer Res. 58(15):3209-3214 (1998); Yoon et al., J. Immunol. 160(7):3170-3179 (1998); Prat et al., J. Cell. Sci. III (Pt2):237-247 (1998); Pitard et al., J. Immunol. Methods 205(2):177-190 (1997); Liautard et al., Cytokine 9(4):233-241 (1997); Carlson et al., J. Biol. Chem. 272(17):11295-11301 (1997); Taryman et al., Neuron 14(4):755-762 (1995); Muller et al., Structure 6(9):1153-1167 (1998); Bartunek et al., Cytokine 8(1):14-20 (1996).

The antibodies as defined for the present invention include derivatives that are modified, i.e., by the covalent attachment of any type of molecule to the antibody such that covalent attachment does not prevent the antibody from generating an anti-idiotypic response. For example, but not by way of limitation, the antibody derivatives include antibodies that have been modified, e.g., by glycosylation, acetylation, pegylation, phosphylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. Any of numerous chemical modifications may be carried out by known techniques including, but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of tunicamycin, etc. Additionally, the derivative may contain one or more non-classical amino acids.

Methods for administering antibodies for therapeutic use is well known to one skilled in the art. In certain embodiments, small particle aerosols of antibodies or fragments thereof may be administered, preferably for treating a respiratory inflammatory disease (See e.g., Piazza et al., J. Infect. Dis., Vol. 166, pp. 1422-1424, 1992; and Brown, Aerosol Science and Technology, Vol. 24, pp. 45-56, 1996). In certain embodiments, antibodies are administered in metered-dose propellant driven aerosols. In preferred embodiments, antibodies are used as inhibitors or antagonists to depress inflammatory diseases or allergen-induced asthmatic responses. In certain embodiments, antibodies may be administered in liposomes, i.e., immunoliposomes (see, e.g., Maruyama et al., Biochim. Biophys. Acta, Vol. 1234, pp. 74-80, 1995). In certain embodiments, immunoconjugates, immunoliposomes or immunomicrospheres containing an agent of the present invention are administered by inhalation.

In some embodiments, the agents may be nucleic acid molecule. Exemplary nucleic acid molecules include aptamers, siRNA, artificial microRNA, interfering RNA or RNAi, dsRNA, ribozymes, antisense oligonucleotides, and DNA expression cassettes encoding said nucleic acid molecules. Preferably, the nucleic acid molecule is an antisense oligonucleotide. Antisense oligonucleotides (ASO) generally inhibit their target by binding target mRNA and sterically blocking expression by obstructing the ribosome. ASOs can also inhibit their target by binding target mRNA thus forming a DNA-RNA hybrid that can be a substance for RNase H. Preferred ASOs include Locked Nucleic Acid (LNA), Peptide Nucleic Acid (PNA), and morpholinos Preferably, the nucleic acid molecule is an RNAi molecule, i.e., RNA interference molecule. Preferred RNAi molecules include siRNA, shRNA, and artificial miRNA. The design and production of siRNA molecules is well known to one of skill in the art (e.g., Hajeri P B, Singh S K. Drug Discov Today. 2009 14(17-18):851-8). The nucleic acid molecule inhibitors may be chemically synthesized and provided directly to cells of interest. The nucleic acid compound may be provided to a cell as part of a gene delivery vehicle. Such a vehicle is preferably a liposome or a viral gene delivery vehicle.

There are a variety of techniques available for introducing nucleic acids into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host. Techniques suitable for the transfer of nucleic acid into mammalian cells in vitro include the use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. The currently preferred in vivo gene transfer techniques include transfection with viral (typically retroviral) vectors and viral coat protein-liposome mediated transfection.

In certain embodiments, an agent may be a hormone, a cytokine, a lymphokine, a growth factor, a chemokine, a cell surface receptor ligand such as a cell surface receptor agonist or antagonist, or a mitogen.

Non-limiting examples of hormones include growth hormone (GH), adrenocorticotropic hormone (ACTH), dehydroepiandrosterone (DHEA), cortisol, epinephrine, thyroid hormone, estrogen, progesterone, testosterone, or combinations thereof.

Non-limiting examples of cytokines include lymphokines (e.g., interferon-γ, IL-2, IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ, leukocyte migration inhibitory factors (T-LIF, B-LIF), lymphotoxin-alpha, macrophage-activating factor (MAF), macrophage migration-inhibitory factor (MIF), neuroleukin, immunologic suppressor factors, transfer factors, or combinations thereof), monokines (e.g., IL-1, TNF-alpha, interferon-α, interferon-β, colony stimulating factors, e.g., CSF2, CSF3, macrophage CSF or GM-CSF, or combinations thereof), chemokines (e.g., beta-thromboglobulin, C chemokines, CC chemokines, CXC chemokines, CX3C chemokines, macrophage inflammatory protein (MIP), or combinations thereof), interleukins (e.g., IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, IL-36, or combinations thereof), and several related signaling molecules, such as tumour necrosis factor (TNF) and interferons (e.g., interferon-α, interferon-β, interferon-γ, interferon-λ, or combinations thereof).

Non-limiting examples of growth factors include those of fibroblast growth factor (FGF) family, bone morphogenic protein (BMP) family, platelet derived growth factor (PDGF) family, transforming growth factor beta (TGFbeta) family, nerve growth factor (NGF) family, epidermal growth factor (EGF) family, insulin related growth factor (IGF) family, hepatocyte growth factor (HGF) family, hematopoietic growth factors (HeGFs), platelet-derived endothelial cell growth factor (PD-ECGF), angiopoietin, vascular endothelial growth factor (VEGF) family, glucocorticoids, or combinations thereof.

Non-limiting examples of mitogens include phytohaemagglutinin (PHA), concanavalin A (conA), lipopolysaccharide (LPS), pokeweed mitogen (PWM), phorbol ester such as phorbol myristate acetate (PMA) with or without ionomycin, or combinations thereof.

Non-limiting examples of cell surface receptors the ligands of which may act as agents include Toll-like receptors (TLRs) (e.g., TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12 or TLR13), CD80, CD86, CD40, CCR7, or C-type lectin receptors.

Genetic Modifying Agents

In certain embodiments, the one or more modulating agents may be a genetic modifying agent. The genetic modifying agent may comprise a CRISPR-Cas system, a zinc finger nuclease system, a TALEN, or a meganuclease.

CRISPR-Cas System

In general, a CRISPR-Cas or CRISPR system as used in herein and in documents, such as WO 2014/093622 (PCT/US2013/074667), refers collectively to transcripts and other elements involved in the expression of or directing the activity of CRISPR-associated (“Cas”) genes, including sequences encoding a Cas gene, a tracr (trans-activating CRISPR) sequence (e.g. tracrRNA or an active partial tracrRNA), a tracr-mate sequence (encompassing a “direct repeat” and a tracrRNA-processed partial direct repeat in the context of an endogenous CRISPR system), a guide sequence (also referred to as a “spacer” in the context of an endogenous CRISPR system), or “RNA(s)” as that term is herein used (e.g., RNA(s) to guide Cas, such as Cas9, e.g. CRISPR RNA and transactivating (tracr) RNA or a single guide RNA (sgRNA) (chimeric RNA)) or other sequences and transcripts from a CRISPR locus. In general, a CRISPR system is characterized by elements that promote the formation of a CRISPR complex at the site of a target sequence (also referred to as a protospacer in the context of an endogenous CRISPR system). See, e.g, Shmakov et al. (2015) “Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems”, Molecular Cell, DOI: dx.doi.org/10.1016/j.molce1.2015.10.008.

Class 1 Systems

The methods, systems, and tools provided herein may be designed for use with Class 1 CRISPR proteins. In certain example embodiments, the Class 1 system may be Type I, Type III or Type IV Cas proteins as described in Makarova et al. “Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants” Nature Reviews Microbiology, 18:67-81 (February 2020)., incorporated in its entirety herein by reference, and particularly as described in FIG. 1 , p. 326. The Class 1 systems typically use a multi-protein effector complex, which can, in some embodiments, include ancillary proteins, such as one or more proteins in a complex referred to as a CRISPR-associated complex for antiviral defense (Cascade), one or more adaptation proteins (e.g. Cas1, Cas2, RNA nuclease), and/or one or more accessory proteins (e.g. Cas 4, DNA nuclease), CRISPR associated Rossman fold (CARF) domain containing proteins, and/or RNA transcriptase. Although Class 1 systems have limited sequence similarity, Class 1 system proteins can be identified by their similar architectures, including one or more Repeat Associated Mysterious Protein (RAMP) family subunits, e.g. Cas 5, Cas6, Cas7. RAMP proteins are characterized by having one or more RNA recognition motif domains. Large subunits (for example cas8 or cas10) and small subunits (for example, cas11) are also typical of Class 1 systems. See, e.g., FIGS. 1 and 2 . Koonin E V, Makarova K S. 2019 Origins and evolution of CRISPR-Cas systems. Phil. Trans. R. Soc. B 374: 20180087, DOI: 10.1098/rstb.2018.0087. In one aspect, Class 1 systems are characterized by the signature protein Cas3. The Cascade in particular Class1 proteins can comprise a dedicated complex of multiple Cas proteins that binds pre-crRNA and recruits an additional Cas protein, for example Cas6 or Cas5, which is the nuclease directly responsible for processing pre-crRNA. In one aspect, the Type I CRISPR protein comprises an effector complex comprises one or more Cas5 subunits and two or more Cas7 subunits. Class 1 subtypes include Type I-A, I-B, I-C, I-U, I-D, I-E, and I-F, Type IV-A and IV-B, and Type III-A, III-C, and III-B. Class 1 systems also include CRISPR-Cas variants, including Type I-A, I-B, I-E, I-F and I-U variants, which can include variants carried by transposons and plasmids, including versions of subtype I-F encoded by a large family of Tn7-like transposon and smaller groups of Tn7-like transposons that encode similarly degraded subtype I-B systems. Peters et al., PNAS 114 (35) (2017); DOI: 10.1073/pnas.1709035114; see also, Makarova et al, the CRISPR Journal, v. 1, n5, FIG. 5 .

Class 2 Systems

In certain embodiments, the compositions, systems, and methods may be designed for use with Class 2 systems. In certain example embodiments, the Class 2 systems may be Type II, Type V, and Type VI systems as described in Makarova et al. “Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants” Nature Reviews Microbiology, 18:67-81 (February 2020), incorporated herein by reference. The distinguishing feature of these types is that their effector complexes consist of a single, large, multi-domain protein. Type V systems differ from Type II effectors (e.g. Cas9) contain two nuclear domains that are each responsible for the cleavage of one strand of the target DNA, with the HNH nuclease inserted inside the Ruv-C like nuclease domain sequence. The Type V systems (e.g. Cas12) only contain a RuvC-like nuclease domain that cleaves both strands. Type VI (Cas13) are unrelated to the effectors of type II and V systems, contain two HEPN domains and target RNA. Cas13 proteins also display collateral activity that is triggered by target recognition. Some Type V systems have also been found to possess this collateral activity two single-stranded DNA in in vitro contexts.

In certain example embodiments, the CRISPR-Cas system comprises a Type II system. In certain example embodiments, the Type II system is a Cas9 system. In certain other example embodiments, the CRISPR-Cas systems is a Type V CRISPR-Cas systems. In certain example embodiments, the Type V CRISPR-Cas is Cas12a, Cas12b, or Cas12c.

Guide Molecules

The modulating agents may comprise one or more guide molecules in CRISPR-Cas systems. As used herein, the term “guide sequence” and “guide molecule” in the context of a CRISPR-Cas system, comprises any polynucleotide sequence having sufficient complementarity with a target nucleic acid sequence to hybridize with the target nucleic acid sequence and direct sequence-specific binding of a nucleic acid-targeting complex to the target nucleic acid sequence. The guide sequences made using the methods disclosed herein may be a full-length guide sequence, a truncated guide sequence, a full-length sgRNA sequence, a truncated sgRNA sequence, or an E+F sgRNA sequence. In some embodiments, the degree of complementarity of the guide sequence to a given target sequence, when optimally aligned using a suitable alignment algorithm, is about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, or more. In certain example embodiments, the guide molecule comprises a guide sequence that may be designed to have at least one mismatch with the target sequence, such that a RNA duplex formed between the guide sequence and the target sequence. Accordingly, the degree of complementarity is preferably less than 99%. For instance, where the guide sequence consists of 24 nucleotides, the degree of complementarity is more particularly about 96% or less. In particular embodiments, the guide sequence is designed to have a stretch of two or more adjacent mismatching nucleotides, such that the degree of complementarity over the entire guide sequence is further reduced. For instance, where the guide sequence consists of 24 nucleotides, the degree of complementarity is more particularly about 96% or less, more particularly, about 92% or less, more particularly about 88% or less, more particularly about 84% or less, more particularly about 80% or less, more particularly about 76% or less, more particularly about 72% or less, depending on whether the stretch of two or more mismatching nucleotides encompasses 2, 3, 4, 5, 6 or 7 nucleotides, etc. In some embodiments, aside from the stretch of one or more mismatching nucleotides, the degree of complementarity, when optimally aligned using a suitable alignment algorithm, is about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, or more. Optimal alignment may be determined with the use of any suitable algorithm for aligning sequences, non-limiting example of which include the Smith-Waterman algorithm, the Needleman-Wunsch algorithm, algorithms based on the Burrows-Wheeler Transform (e.g., the Burrows Wheeler Aligner), ClustalW, Clustal X, BLAT, Novoalign (Novocraft Technologies; available at www.novocraft.com), ELAND (Illumina, San Diego, Calif.), SOAP (available at soap.genomics.org.cn), and Maq (available at maq.sourceforge.net). The ability of a guide sequence (within a nucleic acid-targeting guide RNA) to direct sequence-specific binding of a nucleic acid-targeting complex to a target nucleic acid sequence may be assessed by any suitable assay. For example, the components of a nucleic acid-targeting CRISPR system sufficient to form a nucleic acid-targeting complex, including the guide sequence to be tested, may be provided to a host cell having the corresponding target nucleic acid sequence, such as by transfection with vectors encoding the components of the nucleic acid-targeting complex, followed by an assessment of preferential targeting (e.g., cleavage) within the target nucleic acid sequence, such as by Surveyor assay as described herein. Similarly, cleavage of a target nucleic acid sequence (or a sequence in the vicinity thereof) may be evaluated in a test tube by providing the target nucleic acid sequence, components of a nucleic acid-targeting complex, including the guide sequence to be tested and a control guide sequence different from the test guide sequence, and comparing binding or rate of cleavage at or in the vicinity of the target sequence between the test and control guide sequence reactions. Other assays are possible, and will occur to those skilled in the art. A guide sequence, and hence a nucleic acid-targeting guide RNA may be selected to target any target nucleic acid sequence.

In certain embodiments, the guide sequence or spacer length of the guide molecules is from 15 to 50 nt. In certain embodiments, the spacer length of the guide RNA is at least 15 nucleotides. In certain embodiments, the spacer length is from 15 to 17 nt, e.g., 15, 16, or 17 nt, from 17 to 20 nt, e.g., 17, 18, 19, or 20 nt, from 20 to 24 nt, e.g., 20, 21, 22, 23, or 24 nt, from 23 to 25 nt, e.g., 23, 24, or 25 nt, from 24 to 27 nt, e.g., 24, 25, 26, or 27 nt, from 27 to 30 nt, e.g., 27, 28, 29, or 30 nt, from 30 to 35 nt, e.g., 30, 31, 32, 33, 34, or 35 nt, or 35 nt or longer. In certain example embodiment, the guide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 40, 41, 42, 43, 44, 45, 46, 47 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 nt.

In some embodiments, the guide sequence is an RNA sequence of between 10 to 50 nt in length, but more particularly of about 20 to 30 nt advantageously about 20 nt, 23 to 25 nt or 24 nt. The guide sequence is selected so as to ensure that it hybridizes to the target sequence. This is described more in detail below. Selection can encompass further steps which increase efficacy and specificity.

In some embodiments, the guide sequence has a canonical length (e.g., about 15 to 30 nt) is used to hybridize with the target RNA or DNA. In some embodiments, a guide molecule is longer than the canonical length (e.g., >30 nt) is used to hybridize with the target RNA or DNA, such that a region of the guide sequence hybridizes with a region of the RNA or DNA strand outside of the Cas-guide target complex. This can be of interest where additional modifications, such deamination of nucleotides, are of interest. In alternative embodiments, it is of interest to maintain the limitation of the canonical guide sequence length.

In some embodiments, the sequence of the guide molecule (direct repeat and/or spacer) is selected to reduce the degree of secondary structure within the guide molecule. In some embodiments, about or less than about 75%, 50%, 40%, 30%, 25%, 20%, 15%, 10%, 5%, 1%, or fewer of the nucleotides of the nucleic acid-targeting guide RNA participate in self-complementary base pairing when optimally folded. Optimal folding may be determined by any suitable polynucleotide folding algorithm. Some programs are based on calculating the minimal Gibbs free energy. An example of one such algorithm is mFold, as described by Zuker and Stiegler (Nucleic Acids Res. 9 (1981), 133-148). Another example of folding algorithm is the online webserver RNAfold, developed at the Institute for Theoretical Chemistry at the University of Vienna, using the centroid structure prediction algorithm (see e.g., A. R. Gruber et al., 2008, Cell 106(1): 23-24; and P A Carr and G M Church, 2009, Nature Biotechnology 27(12): 1151-62).

In some embodiments, it is of interest to reduce the susceptibility of the guide molecule to RNA cleavage, such as to cleavage by Cas13. Accordingly, in particular embodiments, the guide molecule is adjusted to avoid cleavage by Cas13 or other RNA-cleaving enzymes.

In certain embodiments, the guide molecule comprises non-naturally occurring nucleic acids and/or non-naturally occurring nucleotides and/or nucleotide analogs, and/or chemical modifications. Preferably, these non-naturally occurring nucleic acids and non-naturally occurring nucleotides are located outside the guide sequence. Non-naturally occurring nucleic acids can include, for example, mixtures of naturally and non-naturally occurring nucleotides. Non-naturally occurring nucleotides and/or nucleotide analogs may be modified at the ribose, phosphate, and/or base moiety. In an embodiment of the invention, a guide nucleic acid comprises ribonucleotides and non-ribonucleotides. In one such embodiment, a guide comprises one or more ribonucleotides and one or more deoxyribonucleotides. In an embodiment of the invention, the guide comprises one or more non-naturally occurring nucleotide or nucleotide analog such as a nucleotide with phosphorothioate linkage, a locked nucleic acid (LNA) nucleotides comprising a methylene bridge between the 2′ and 4′ carbons of the ribose ring, or bridged nucleic acids (BNA). Other examples of modified nucleotides include 2′-O-methyl analogs, 2′-deoxy analogs, or 2′-fluoro analogs. Further examples of modified bases include, but are not limited to, 2-aminopurine, 5-bromo-uridine, pseudouridine, inosine, 7-methylguanosine. Examples of guide RNA chemical modifications include, without limitation, incorporation of 2′-O-methyl (M), 2′-O-methyl 3′phosphorothioate (MS), S-constrained ethyl(cEt), or 2′-O-methyl 3′thioPACE (MSP) at one or more terminal nucleotides. Such chemically modified guides can comprise increased stability and increased activity as compared to unmodified guides, though on-target vs. off-target specificity is not predictable. (See, Hendel, 2015, Nat Biotechnol. 33(9):985-9, doi: 10.1038/nbt.3290, published online 29 Jun. 2015 Ragdarm et al., 0215, PNAS, E7110-E7111; Allerson et al., J. Med. Chem. 2005, 48:901-904; Bramsen et al., Front. Genet., 2012, 3:154; Deng et al., PNAS, 2015, 112:11870-11875; Sharma et al., Med Chem Comm., 2014, 5:1454-1471; Hendel et al., Nat. Biotechnol. (2015) 33(9): 985-989; Li et al., Nature Biomedical Engineering, 2017, 1, 0066 DOI:10.1038/s41551-017-0066). In some embodiments, the 5′ and/or 3′ end of a guide RNA is modified by a variety of functional moieties including fluorescent dyes, polyethylene glycol, cholesterol, proteins, or detection tags. (See Kelly et al., 2016, J. Biotech. 233:74-83). In certain embodiments, a guide comprises ribonucleotides in a region that binds to a target RNA and one or more deoxyribonucleotides and/or nucleotide analogs in a region that binds to Cas13. In an embodiment of the invention, deoxyribonucleotides and/or nucleotide analogs are incorporated in engineered guide structures, such as, without limitation, stem-loop regions, and the seed region. For Cas13 guide, in certain embodiments, the modification is not in the 5′-handle of the stem-loop regions. Chemical modification in the 5′-handle of the stem-loop region of a guide may abolish its function (see Li, et al., Nature Biomedical Engineering, 2017, 1:0066). In certain embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, or 75 nucleotides of a guide is chemically modified. In some embodiments, 3-5 nucleotides at either the 3′ or the 5′ end of a guide is chemically modified. In some embodiments, only minor modifications are introduced in the seed region, such as 2′-F modifications. In some embodiments, 2′-F modification is introduced at the 3′ end of a guide. In certain embodiments, three to five nucleotides at the 5′ and/or the 3′ end of the guide are chemically modified with 2′-O-methyl (M), 2′-O-methyl 3′ phosphorothioate (MS), S-constrained ethyl(cEt), or 2′-O-methyl 3′ thioPACE (MSP). Such modification can enhance genome editing efficiency (see Hendel et al., Nat. Biotechnol. (2015) 33(9): 985-989). In certain embodiments, all of the phosphodiester bonds of a guide are substituted with phosphorothioates (PS) for enhancing levels of gene disruption. In certain embodiments, more than five nucleotides at the 5′ and/or the 3′ end of the guide are chemically modified with 2′-O-Me, 2′-F or S-constrained ethyl(cEt). Such chemically modified guide can mediate enhanced levels of gene disruption (see Ragdarm et al., 0215, PNAS, E7110-E7111). In an embodiment of the invention, a guide is modified to comprise a chemical moiety at its 3′ and/or 5′ end. Such moieties include, but are not limited to, amine, azide, alkyne, thio, dibenzocyclooctyne (DBCO), or Rhodamine. In certain embodiment, the chemical moiety is conjugated to the guide by a linker, such as an alkyl chain. In certain embodiments, the chemical moiety of the modified guide can be used to attach the guide to another molecule, such as DNA, RNA, protein, or nanoparticles. Such chemically modified guide can be used to identify or enrich cells generically edited by a CRISPR system (See Lee et al., eLife, 2017, 6:e25312, D01:10.7554).

In some embodiments, the modification to the guide is a chemical modification, an insertion, a deletion or a split. In some embodiments, the chemical modification includes, but is not limited to, incorporation of 2′-O-methyl (M) analogs, 2′-deoxy analogs, 2-thiouridine analogs, N6-methyladenosine analogs, 2′-fluoro analogs, 2-aminopurine, 5-bromo-uridine, pseudouridine (Ψ), N1-methylpseudouridine (me1Ψ), 5-methoxyuridine (5moU), inosine, 7-methylguanosine, 2′-O-methyl 3′phosphorothioate (MS), S-constrained ethyl(cEt), phosphorothioate (PS), or 2′-O-methyl 3′thioPACE (MSP). In some embodiments, the guide comprises one or more of phosphorothioate modifications. In certain embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 25 nucleotides of the guide are chemically modified. In certain embodiments, one or more nucleotides in the seed region are chemically modified. In certain embodiments, one or more nucleotides in the 3′-terminus are chemically modified. In certain embodiments, none of the nucleotides in the 5′-handle is chemically modified. In some embodiments, the chemical modification in the seed region is a minor modification, such as incorporation of a 2′-fluoro analog. In a specific embodiment, one nucleotide of the seed region is replaced with a 2′-fluoro analog. In some embodiments, 5 to 10 nucleotides in the 3′-terminus are chemically modified. Such chemical modifications at the 3′-terminus of the Cas13 CrRNA may improve Cas13 activity. In a specific embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides in the 3′-terminus are replaced with 2′-fluoro analogues. In a specific embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides in the 3′-terminus are replaced with 2′-O-methyl (M) analogs.

In some embodiments, the loop of the 5′-handle of the guide is modified. In some embodiments, the loop of the 5′-handle of the guide is modified to have a deletion, an insertion, a split, or chemical modifications. In certain embodiments, the modified loop comprises 3, 4, or 5 nucleotides. In certain embodiments, the loop comprises the sequence of UCUU, UUUU, UAUU, or UGUU.

In some embodiments, the guide molecule forms a stemloop with a separate non-covalently linked sequence, which can be DNA or RNA. In particular embodiments, the sequences forming the guide are first synthesized using the standard phosphoramidite synthetic protocol (Herdewijn, P., ed., Methods in Molecular Biology Col 288, Oligonucleotide Synthesis: Methods and Applications, Humana Press, New Jersey (2012)). In some embodiments, these sequences can be functionalized to contain an appropriate functional group for ligation using the standard protocol known in the art (Hermanson, G. T., Bioconjugate Techniques, Academic Press (2013)). Examples of functional groups include, but are not limited to, hydroxyl, amine, carboxylic acid, carboxylic acid halide, carboxylic acid active ester, aldehyde, carbonyl, chlorocarbonyl, imidazolylcarbonyl, hydrozide, semicarbazide, thio semicarbazide, thiol, maleimide, haloalkyl, sufonyl, ally, propargyl, diene, alkyne, and azide. Once this sequence is functionalized, a covalent chemical bond or linkage can be formed between this sequence and the direct repeat sequence. Examples of chemical bonds include, but are not limited to, those based on carbamates, ethers, esters, amides, imines, amidines, aminotrizines, hydrozone, disulfides, thioethers, thioesters, phosphorothioates, phosphorodithioates, sulfonamides, sulfonates, fulfones, sulfoxides, ureas, thioureas, hydrazide, oxime, triazole, photolabile linkages, C—C bond forming groups such as Diels-Alder cyclo-addition pairs or ring-closing metathesis pairs, and Michael reaction pairs.

In some embodiments, these stem-loop forming sequences can be chemically synthesized. In some embodiments, the chemical synthesis uses automated, solid-phase oligonucleotide synthesis machines with 2′-acetoxyethyl orthoester (2′-ACE) (Scaringe et al., J. Am. Chem. Soc. (1998) 120: 11820-11821; Scaringe, Methods Enzymol. (2000) 317: 3-18) or 2′-thionocarbamate (2′-TC) chemistry (Dellinger et al., J. Am. Chem. Soc. (2011) 133: 11540-11546; Hendel et al., Nat. Biotechnol. (2015) 33:985-989).

In certain embodiments, the guide molecule comprises (1) a guide sequence capable of hybridizing to a target locus and (2) a tracr mate or direct repeat sequence whereby the direct repeat sequence is located upstream (i.e., 5′) from the guide sequence. In a particular embodiment the seed sequence (i.e. the sequence essential critical for recognition and/or hybridization to the sequence at the target locus) of the guide sequence is approximately within the first 10 nucleotides of the guide sequence.

In a particular embodiment the guide molecule comprises a guide sequence linked to a direct repeat sequence, wherein the direct repeat sequence comprises one or more stem loops or optimized secondary structures. In particular embodiments, the direct repeat has a minimum length of 16 nts and a single stem loop. In further embodiments the direct repeat has a length longer than 16 nts, preferably more than 17 nts, and has more than one stem loop or optimized secondary structures. In particular embodiments the guide molecule comprises or consists of the guide sequence linked to all or part of the natural direct repeat sequence. A typical Type V or Type VI CRISPR-cas guide molecule comprises (in 3′ to 5′ direction or in 5′ to 3′ direction): a guide sequence a first complimentary stretch (the “repeat”), a loop (which is typically 4 or 5 nucleotides long), a second complimentary stretch (the “anti-repeat” being complimentary to the repeat), and a poly A (often poly U in RNA) tail (terminator). In certain embodiments, the direct repeat sequence retains its natural architecture and forms a single stem loop. In particular embodiments, certain aspects of the guide architecture can be modified, for example by addition, subtraction, or substitution of features, whereas certain other aspects of guide architecture are maintained. Preferred locations for engineered guide molecule modifications, including but not limited to insertions, deletions, and substitutions include guide termini and regions of the guide molecule that are exposed when complexed with the CRISPR-Cas protein and/or target, for example the stemloop of the direct repeat sequence.

In particular embodiments, the stem comprises at least about 4 bp comprising complementary X and Y sequences, although stems of more, e.g., 5, 6, 7, 8, 9, 10, 11 or 12 or fewer, e.g., 3, 2, base pairs are also contemplated. Thus, for example X2-10 and Y2-10 (wherein X and Y represent any complementary set of nucleotides) may be contemplated. In one aspect, the stem made of the X and Y nucleotides, together with the loop will form a complete hairpin in the overall secondary structure; and, this may be advantageous and the number of base pairs can be any amount that forms a complete hairpin. In one aspect, any complementary X:Y basepairing sequence (e.g., as to length) is tolerated, so long as the secondary structure of the entire guide molecule is preserved. In one aspect, the loop that connects the stem made of X:Y basepairs can be any sequence of the same length (e.g., 4 or 5 nucleotides) or longer that does not interrupt the overall secondary structure of the guide molecule. In one aspect, the stemloop can further comprise, e.g. an MS2 aptamer. In one aspect, the stem comprises about 5-7 bp comprising complementary X and Y sequences, although stems of more or fewer basepairs are also contemplated. In one aspect, non-Watson Crick basepairing is contemplated, where such pairing otherwise generally preserves the architecture of the stem loop at that position.

In particular embodiments the natural hairpin or stem loop structure of the guide molecule is extended or replaced by an extended stem loop. It has been demonstrated that extension of the stem can enhance the assembly of the guide molecule with the CRISPR-Cas protein (Chen et al. Cell. (2013); 155(7): 1479-1491). In particular embodiments the stem of the stemloop is extended by at least 1, 2, 3, 4, 5 or more complementary basepairs (i.e. corresponding to the addition of 2, 4, 6, 8, 10 or more nucleotides in the guide molecule). In particular embodiments these are located at the end of the stem, adjacent to the loop of the stemloop.

In particular embodiments, the susceptibility of the guide molecule to RNAses or to decreased expression can be reduced by slight modifications of the sequence of the guide molecule which do not affect its function. For instance, in particular embodiments, premature termination of transcription, such as premature transcription of U6 Pol-III, can be removed by modifying a putative Pol-III terminator (4 consecutive U's) in the guide molecules sequence. Where such sequence modification is required in the stemloop of the guide molecule, it is preferably ensured by a basepair flip.

In a particular embodiment, the direct repeat may be modified to comprise one or more protein-binding RNA aptamers. In a particular embodiment, one or more aptamers may be included such as part of optimized secondary structure. Such aptamers may be capable of binding a bacteriophage coat protein as detailed further herein.

In some embodiments, the guide molecule forms a duplex with a target RNA comprising at least one target cytosine residue to be edited. Upon hybridization of the guide RNA molecule to the target RNA, the cytidine deaminase binds to the single strand RNA in the duplex made accessible by the mismatch in the guide sequence and catalyzes deamination of one or more target cytosine residues comprised within the stretch of mismatching nucleotides.

A guide sequence, and hence a nucleic acid-targeting guide RNA may be selected to target any target nucleic acid sequence. The target sequence may be mRNA.

In certain embodiments, the target sequence should be associated with a PAM (protospacer adjacent motif) or PFS (protospacer flanking sequence or site); that is, a short sequence recognized by the CRISPR complex. Depending on the nature of the CRISPR-Cas protein, the target sequence should be selected such that its complementary sequence in the DNA duplex (also referred to herein as the non-target sequence) is upstream or downstream of the PAM. In the embodiments of the present invention where the CRISPR-Cas protein is a Cas13 protein, the complementary sequence of the target sequence is downstream or 3′ of the PAM or upstream or 5′ of the PAM. The precise sequence and length requirements for the PAM differ depending on the Cas13 protein used, but PAMs are typically 2-5 base pair sequences adjacent the protospacer (that is, the target sequence). Examples of the natural PAM sequences for different Cas13 orthologues are provided herein below and the skilled person will be able to identify further PAM sequences for use with a given Cas13 protein.

Further, engineering of the PAM Interacting (PI) domain may allow programing of PAM specificity, improve target site recognition fidelity, and increase the versatility of the CRISPR-Cas protein, for example as described for Cas9 in Kleinstiver B P et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015 Jul. 23; 523(7561):481-5. doi: 10.1038/nature14592. As further detailed herein, the skilled person will understand that Cas13 proteins may be modified analogously.

In particular embodiment, the guide is an escorted guide. By “escorted” is meant that the CRISPR-Cas system or complex or guide is delivered to a selected time or place within a cell, so that activity of the CRISPR-Cas system or complex or guide is spatially or temporally controlled. For example, the activity and destination of the 3 CRISPR-Cas system or complex or guide may be controlled by an escort RNA aptamer sequence that has binding affinity for an aptamer ligand, such as a cell surface protein or other localized cellular component. Alternatively, the escort aptamer may for example be responsive to an aptamer effector on or in the cell, such as a transient effector, such as an external energy source that is applied to the cell at a particular time.

The escorted CRISPR-Cas systems or complexes have a guide molecule with a functional structure designed to improve guide molecule structure, architecture, stability, genetic expression, or any combination thereof. Such a structure can include an aptamer.

Aptamers are biomolecules that can be designed or selected to bind tightly to other ligands, for example using a technique called systematic evolution of ligands by exponential enrichment (SELEX; Tuerk C, Gold L: “Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.” Science 1990, 249:505-510). Nucleic acid aptamers can for example be selected from pools of random-sequence oligonucleotides, with high binding affinities and specificities for a wide range of biomedically relevant targets, suggesting a wide range of therapeutic utilities for aptamers (Keefe, Anthony D., Supriya Pai, and Andrew Ellington. “Aptamers as therapeutics.” Nature Reviews Drug Discovery 9.7 (2010): 537-550). These characteristics also suggest a wide range of uses for aptamers as drug delivery vehicles (Levy-Nissenbaum, Etgar, et al. “Nanotechnology and aptamers: applications in drug delivery.” Trends in Biotechnology 26.8 (2008): 442-449; and, Hicke B J, Stephens A W. “Escort aptamers: a delivery service for diagnosis and therapy.” J Clin Invest 2000, 106:923-928.). Aptamers may also be constructed that function as molecular switches, responding to a que by changing properties, such as RNA aptamers that bind fluorophores to mimic the activity of green fluorescent protein (Paige, Jeremy S., Karen Y. Wu, and Samie R. Jaffrey. “RNA mimics of green fluorescent protein.” Science 333.6042 (2011): 642-646). It has also been suggested that aptamers may be used as components of targeted siRNA therapeutic delivery systems, for example targeting cell surface proteins (Zhou, Jiehua, and John J. Rossi. “Aptamer-targeted cell-specific RNA interference.” Silence 1.1 (2010): 4).

Accordingly, in particular embodiments, the guide molecule is modified, e.g., by one or more aptamer(s) designed to improve guide molecule delivery, including delivery across the cellular membrane, to intracellular compartments, or into the nucleus. Such a structure can include, either in addition to the one or more aptamer(s) or without such one or more aptamer(s), moiety(ies) so as to render the guide molecule deliverable, inducible or responsive to a selected effector. The invention accordingly comprehends a guide molecule that responds to normal or pathological physiological conditions, including without limitation pH, hypoxia, O₂ concentration, temperature, protein concentration, enzymatic concentration, lipid structure, light exposure, mechanical disruption (e.g. ultrasound waves), magnetic fields, electric fields, or electromagnetic radiation. Inducible systems and energy application can be as described for example, in International Patent Publication WO2019232542 at [0275]-[0302], incorporated herein by reference.

In particular embodiments, the guide molecule is modified by a secondary structure to increase the specificity of the CRISPR-Cas system and the secondary structure can protect against exonuclease activity and allow for 5′ additions to the guide sequence also referred to herein as a protected guide molecule.

In one aspect, the invention provides for hybridizing a “protector RNA” to a sequence of the guide molecule, wherein the “protector RNA” is an RNA strand complementary to the 3′ end of the guide molecule to thereby generate a partially double-stranded guide RNA. In an embodiment of the invention, protecting mismatched bases (i.e. the bases of the guide molecule which do not form part of the guide sequence) with a perfectly complementary protector sequence decreases the likelihood of target RNA binding to the mismatched basepairs at the 3′ end. In particular embodiments of the invention, additional sequences comprising an extended length may also be present within the guide molecule such that the guide comprises a protector sequence within the guide molecule. This “protector sequence” ensures that the guide molecule comprises a “protected sequence” in addition to an “exposed sequence” (comprising the part of the guide sequence hybridizing to the target sequence). In particular embodiments, the guide molecule is modified by the presence of the protector guide to comprise a secondary structure such as a hairpin. Advantageously there are three or four to thirty or more, e.g., about 10 or more, contiguous base pairs having complementarity to the protected sequence, the guide sequence or both. It is advantageous that the protected portion does not impede thermodynamics of the CRISPR-Cas system interacting with its target. By providing such an extension including a partially double stranded guide molecule, the guide molecule is considered protected and results in improved specific binding of the CRISPR-Cas complex, while maintaining specific activity.

In particular embodiments, use is made of a truncated guide (tru-guide), i.e., a guide molecule which comprises a guide sequence which is truncated in length with respect to the canonical guide sequence length. As described by Nowak et al. (Nucleic Acids Res (2016) 44 (20): 9555-9564), such guides may allow catalytically active CRISPR-Cas enzyme to bind its target without cleaving the target RNA. In particular embodiments, a truncated guide is used which allows the binding of the target but retains only nickase activity of the CRISPR-Cas enzyme.

In addition to the above CRISPR-Cas systems, the CRISPR-Cas may be a base editor version, thereof i.e. a catalytically dead Cas linked or fused to a nucleotide deaminase domain. The Cas may be a RNA-binding (e.g. Type VI) on DNA-binding Cas (Type II or V). In certain embodiments, the compositions, systems, and methods may be designed for use with Class 2 systems. In certain example embodiments, the Class 2 systems may be Type II, Type V, and Type VI systems as described in Makarova et al. “Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants” Nature Reviews Microbiology, 18:67-81 (February 2020), incorporated herein by reference. The distinguishing feature of these types is that their effector complexes consist of a single, large, multi-domain protein. Type V systems differ from Type II effectors (e.g. Cas9) contain two nuclear domains that are each responsible for the cleavage of one strand of the target DNA, with the HNH nuclease inserted inside the Ruv-C like nuclease domain sequence. The Type V systems (e.g. Cas12) only contain a RuvC-like nuclease domain that cleaves both strands. Type VI (Cas13) are unrelated to the effectors of type II and V systems, contain two HEPN domains and target RNA. Cas13 proteins also display collateral activity that is triggered by target recognition. Some Type V systems have also been found to possess this collateral activity two single-stranded DNA in in vitro contexts.

In certain example embodiments, the CRISPR-Cas system comprises a Type II system. In certain example embodiments, the Type II system is a Cas9 system. In certain other example embodiments, the CRISPR-Cas systems is a Type V CRISPR-Cas systems. In certain example embodiments, the Type V CRISPR-Cas is Cas12a, Cas12b, or Cas12c.

The present invention also contemplates use of the CRISPR-Cas system and the base editor described herein, for treatment in a variety of diseases and disorders. In some embodiments, the invention described herein relates to a method for therapy in which cells are edited ex vivo by CRISPR or the base editor to modulate at least one gene, with subsequent administration of the edited cells to a patient in need thereof. In some embodiments, the editing involves knocking in, knocking out or knocking down expression of at least one target gene in a cell. In particular embodiments, the editing inserts an exogenous, gene, minigene or sequence, which may comprise one or more exons and introns or natural or synthetic introns into the locus of a target gene, a hot-spot locus, a safe harbor locus of the gene genomic locations where new genes or genetic elements can be introduced without disrupting the expression or regulation of adjacent genes, or correction by insertions or deletions one or more mutations in DNA sequences that encode regulatory elements of a target gene. In some embodiment, the editing comprise introducing one or more point mutations in a nucleic acid (e.g., a genomic DNA) in a target cell.

The present disclosure also provides for a base editing system. In general, such a system may comprise a deaminase (e.g., an adenosine deaminase or cytidine deaminase) fused with a Cas protein. The Cas protein may be a dead Cas protein or a Cas nickase protein. In certain examples, the system comprises a mutated form of an adenosine deaminase fused with a dead CRISPR-Cas or CRISPR-Cas nickase. The mutated form of the adenosine deaminase may have both adenosine deaminase and cytidine deaminase activities.

In one aspect, the present disclosure provides an engineered adenosine deaminase. The engineered adenosine deaminase may comprise one or more mutations herein. In some embodiments, the engineered adenosine deaminase has cytidine deaminase activity. In certain examples, the engineered adenosine deaminase has both cytidine deaminase activity and adenosine deaminase. In some cases, the modifications by base editors herein may be used for targeting post-translational signaling or catalysis.

In one aspect, the invention provides a method of modifying or editing a target transcript in a eukaryotic cell. In some embodiments, the method comprises allowing a CRISPR-Cas effector module complex to bind to the target polynucleotide to effect RNA base editing, wherein the CRISPR-Cas effector module complex comprises a Cas effector module complexed with a guide sequence hybridized to a target sequence within said target polynucleotide, wherein said guide sequence is linked to a direct repeat sequence. In some embodiments, the Cas effector module comprises a catalytically inactive CRISPR-Cas protein. In some embodiments, the guide sequence is designed to introduce one or more mismatches to the RNA/RNA duplex formed between the target sequence and the guide sequence. In particular embodiments, the mismatch is an A-C mismatch. In some embodiments, the Cas effector may associate with one or more functional domains (e.g. via fusion protein or suitable linkers). In some embodiments, the effector domain comprises one or more cytidine or adenosine deaminases that mediate endogenous editing of via hydrolytic deamination. In particular embodiments, the effector domain comprises the adenosine deaminase acting on RNA (ADAR) family of enzymes. In particular embodiments, the adenosine deaminase protein or catalytic domain thereof is capable of deaminating adenosine or cytidine in RNA or is an RNA specific adenosine deaminase and/or is a bacterial, human, cephalopod, or Drosophila adenosine deaminase protein or catalytic domain thereof, preferably TadA, more preferably ADAR, optionally huADAR, optionally (hu)ADAR1 or (hu)ADAR2, preferably huADAR2 or catalytic domain thereof. See, e.g. Levy et al., doi:10.1038/s41551-019-0501-5, Rees et al, doi: 10.1038/s41467-019-09983-4; Komor et al, m Nature 533(7603), 420-424, Gaudellim et al, Nature 551 (7681), 464-471, Lee, et al., Nature Commun. 9:4804 1-5(2018), Song et al., Biomed End. 36, 536-539 (2018), Lee et al., Sci. Rep. 9, 1662 (2019), Thuronyi, et al., Nat. Biotechnol. 37, 1070-1079 (2019), Anzalone, et al., nature 576 149-157 (2019), and Richter et al., Nat Biotechnol in press (2020), all incorporated herein by reference. Reference is also made to International Patent Publication Nos. WO 2019/005884, WO 2019/005886, WO 2020/028555, WO 2019/060746, WO 2019/071048, WO 2019/084063, and Abudayyeh et al., Science 365:6451, 382-386, doi: 10.1126/science.aax7063, incorporated herein by reference.

TALE Systems

The modulating agents may be one or more components of a TALE system, or nucleic acids encoding thereof. As disclosed herein editing can be made by way of the transcription activator-like effector nucleases (TALENs) system. Transcription activator-like effectors (TALEs) can be engineered to bind practically any desired DNA sequence. Exemplary methods of genome editing using the TALEN system can be found for example in Cermak T. Doyle E L. Christian M. Wang L. Zhang Y. Schmidt C, et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 2011; 39:e82; Zhang F. Cong L. Lodato S. Kosuri S. Church G M. Arlotta P Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat Biotechnol. 2011; 29:149-153 and U.S. Pat. Nos. 8,450,471, 8,440,431 and 8,440,432, all of which are specifically incorporated by reference. Further description of TALE systems are as described in [0340]-[0351] of WO 2019232542, incorporated herein by reference.

As described in Zhang et al., Nature Biotechnology 29:149-153 (2011), TALE polypeptide binding efficiency may be increased by including amino acid sequences from the “capping regions” that are directly N-terminal or C-terminal of the DNA binding region of naturally occurring TALEs into the engineered TALEs at positions N-terminal or C-terminal of the engineered TALE DNA binding region. Thus, in certain embodiments, the TALE polypeptides described herein further comprise an N-terminal capping region and/or a C-terminal capping region.

As used herein the predetermined “N-terminus” to “C terminus” orientation of the N-terminal capping region, the DNA binding domain comprising the repeat TALE monomers and the C-terminal capping region provide structural basis for the organization of different domains in the d-TALEs or polypeptides of the invention, fragments of the N-terminal and/or C-terminal capping regions can also be utilized with the TALE polypeptides.

In some embodiments described herein, the TALE polypeptides of the invention include a nucleic acid binding domain linked to the one or more effector domains. The terms “effector domain” or “regulatory and functional domain” refer to a polypeptide sequence that has an activity other than binding to the nucleic acid sequence recognized by the nucleic acid binding domain. By combining a nucleic acid binding domain with one or more effector domains, the polypeptides of the invention may be used to target the one or more functions or activities mediated by the effector domain to a particular target DNA sequence to which the nucleic acid binding domain specifically binds.

In some embodiments of the TALE polypeptides described herein, the activity mediated by the effector domain is a biological activity. For example, in some embodiments the effector domain is a transcriptional inhibitor (i.e., a repressor domain), such as an mSin interaction domain (SID). SID4× domain or a Krüppel-associated box (KRAB) or fragments of the KRAB domain. In some embodiments the effector domain is an enhancer of transcription (i.e. an activation domain), such as the VP16, VP64 or p65 activation domain. In some embodiments, the nucleic acid binding is linked, for example, with an effector domain that includes but is not limited to a transposase, integrase, recombinase, resolvase, invertase, protease, DNA methyltransferase, DNA demethylase, histone acetylase, histone deacetylase, nuclease, transcriptional repressor, transcriptional activator, transcription factor recruiting, protein nuclear-localization signal or cellular uptake signal.

In some embodiments, the effector domain is a protein domain which exhibits activities which include but are not limited to transposase activity, integrase activity, recombinase activity, resolvase activity, invertase activity, protease activity, DNA methyltransferase activity, DNA demethylase activity, histone acetylase activity, histone deacetylase activity, nuclease activity, nuclear-localization signaling activity, transcriptional repressor activity, transcriptional activator activity, transcription factor recruiting activity, or cellular uptake signaling activity. Other preferred embodiments of the invention may include any combination the activities described herein.

Zn-Finger Nucleases

The one or more agents may comprise Zn-finger nucleases or nucleic acids encoding thereof. Other preferred tools for genome editing for use in the context of this invention include zinc finger systems and TALE systems. One type of programmable DNA-binding domain is provided by artificial zinc-finger (ZF) technology, which involves arrays of ZF modules to target new DNA-binding sites in the genome. Each finger module in a ZF array targets three DNA bases. A customized array of individual zinc finger domains is assembled into a ZF protein (ZFP).

ZFPs can comprise a functional domain. The first synthetic zinc finger nucleases (ZFNs) were developed by fusing a ZF protein to the catalytic domain of the Type IIS restriction enzyme FokI. (Kim, Y. G. et al., 1994, Chimeric restriction endonuclease, Proc. Natl. Acad. Sci. U.S.A. 91, 883-887; Kim, Y. G. et al., 1996, Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc. Natl. Acad. Sci. U.S.A. 93, 1156-1160). Increased cleavage specificity can be attained with decreased off target activity by use of paired ZFN heterodimers, each targeting different nucleotide sequences separated by a short spacer. (Doyon, Y. et al., 2011, Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat. Methods 8, 74-79). ZFPs can also be designed as transcription activators and repressors and have been used to target many genes in a wide variety of organisms. Exemplary methods of genome editing using ZFNs can be found for example in U.S. Pat. Nos. 6,534,261, 6,607,882, 6,746,838, 6,794,136, 6,824,978, 6,866,997, 6,933,113, 6,979,539, 7,013,219, 7,030,215, 7,220,719, 7,241,573, 7,241,574, 7,585,849, 7,595,376, 6,903,185, and 6,479,626, all of which are specifically incorporated by reference.

Meganucleases

As disclosed herein editing can be made by way of meganucleases, which are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs). Exemplary method for using meganucleases can be found in U.S. Pat. Nos. 8,163,514, 8,133,697, 8,021,867, 8,119,361, 8,119,381, 8,124,369, and 8,129,134, which are specifically incorporated by reference.

In certain embodiments, any of the nucleases, including the modified nucleases as described herein, may be used in the methods, compositions, and kits according to the invention. In particular embodiments, nuclease activity of an unmodified nuclease may be compared with nuclease activity of any of the modified nucleases as described herein, e.g. to compare for instance off-target or on-target effects. Alternatively, nuclease activity (or a modified activity as described herein) of different modified nucleases may be compared, e.g. to compare for instance off-target or on-target effects.

Other Example Types of Modulating Agents

Also provided herein are compositions for use in carrying out the methods of the invention. More particularly, non-naturally occurring or engineered compositions are provided which comprise one or more of the elements required to ensure genomic perturbation. In particular embodiments, the compositions comprise one or more of the (modified) DNA binding protein, and/or a guide RNA. In particular embodiments, the composition comprises a vector. In an aspect, the vector can target liver macrophages specifically. In an aspect the vector can be configured to target hepatoctyes such that the agent that stimulates macrophage Wnt signaling (modulating agent) is released at the site of injury. In this regard, hepatic delivery is known in the art and can be adapted for the uses as described herein. See, e.g. Mishra et al., BioMed Res Int'l (2013) doi: 10.1155/2013/382184, Huang et al., Bioconjugate Chem. 2017, 28, 2, 283-29; Zimmerman et al., Molecular Therapy, 25: 1, 4 Jan. 2017, Pages 71-78, doi:10.1016/j.ymthe.2003.09.009, incorporated herein by reference.

In further particular embodiments, the vector comprises a polynucleotide encoding a gRNA. In particular embodiments, the vector comprises two or more guide RNAs. The two or more guide RNAs may target a different target (so as to ensure multiplex targeting) or the same target, in which case the different guide RNAs will target different sequences within the same target sequence. Where provided in a vector the different guide RNAs may be under common control of the same promotor, or may be each be under control of the same or different promoters.

In certain embodiments, a modulating agent may comprise silencing one or more endogenous genes. As used herein, “gene silencing” or “gene silenced” in reference to an activity of an RNAi molecule, for example a siRNA or miRNA refers to a decrease in the mRNA level in a cell for a target gene by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 99%, about 100% of the mRNA level found in the cell without the presence of the miRNA or RNA interference molecule. In one preferred embodiment, the mRNA levels are decreased by at least about 70%, about 80%, about 90%, about 95%, about 99%, about 100%.

As used herein, the term “RNAi” refers to any type of interfering RNA, including but not limited to, siRNAi, shRNAi, endogenous microRNA and artificial microRNA. For instance, it includes sequences previously identified as siRNA, regardless of the mechanism of down-stream processing of the RNA (i.e. although siRNAs are believed to have a specific method of in vivo processing resulting in the cleavage of mRNA, such sequences can be incorporated into the vectors in the context of the flanking sequences described herein). The term “RNAi” can include both gene silencing RNAi molecules, and also RNAi effector molecules which activate the expression of a gene.

As used herein, a “siRNA” refers to a nucleic acid that forms a double stranded RNA, which double stranded RNA has the ability to reduce or inhibit expression of a gene or target gene when the siRNA is present or expressed in the same cell as the target gene. The double stranded RNA siRNA can be formed by the complementary strands. In one embodiment, a siRNA refers to a nucleic acid that can form a double stranded siRNA. The sequence of the siRNA can correspond to the full-length target gene, or a subsequence thereof. Typically, the siRNA is at least about 15-50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is about 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length, preferably about 19-30 base nucleotides, preferably about 20-25 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length).

As used herein “shRNA” or “small hairpin RNA” (also called stem loop) is a type of siRNA. In one embodiment, these shRNAs are composed of a short, e.g. about 19 to about 25 nucleotide, antisense strand, followed by a nucleotide loop of about 5 to about 9 nucleotides, and the analogous sense strand. Alternatively, the sense strand can precede the nucleotide loop structure and the antisense strand can follow.

The terms “microRNA” or “miRNA” are used interchangeably herein are endogenous RNAs, some of which are known to regulate the expression of protein-coding genes at the posttranscriptional level. Endogenous microRNAs are small RNAs naturally present in the genome that are capable of modulating the productive utilization of mRNA. The term artificial microRNA includes any type of RNA sequence, other than endogenous microRNA, which is capable of modulating the productive utilization of mRNA. MicroRNA sequences have been described in publications such as Lim, et al., Genes & Development, 17, p. 991-1008 (2003), Lim et al Science 299, 1540 (2003), Lee and Ambros Science, 294, 862 (2001), Lau et al., Science 294, 858-861 (2001), Lagos-Quintana et al, Current Biology, 12, 735-739 (2002), Lagos Quintana et al, Science 294, 853-857 (2001), and Lagos-Quintana et al, RNA, 9, 175-179 (2003), which are incorporated by reference. Multiple microRNAs can also be incorporated into a precursor molecule. Furthermore, miRNA-like stem-loops can be expressed in cells as a vehicle to deliver artificial miRNAs and short interfering RNAs (siRNAs) for the purpose of modulating the expression of endogenous genes through the miRNA and or RNAi pathways.

As used herein, “double stranded RNA” or “dsRNA” refers to RNA molecules that are comprised of two strands. Double-stranded molecules include those comprised of a single RNA molecule that doubles back on itself to form a two-stranded structure. For example, the stem loop structure of the progenitor molecules from which the single-stranded miRNA is derived, called the pre-miRNA (Bartel et al. 2004. Cell 1 16:281-297), comprises a dsRNA molecule.

In certain embodiments, a modulant may comprise (i) a DNA-binding portion configured to specifically bind to the endogenous gene and (ii) an effector domain mediating a biological activity.

In certain embodiments, the DNA-binding portion may comprise a zinc finger protein or DNA-binding domain thereof, a transcription activator-like effector (TALE) protein or DNA-binding domain thereof, or an RNA-guided protein or DNA-binding domain thereof.

In certain embodiments, the DNA-binding portion may comprise (i) Cas9 or Cpf1 or any Cas protein described herein modified to eliminate its nuclease activity, or (ii) DNA-binding domain of Cas9 or Cpf1 or any Cas protein described herein.

In some embodiments, the effector domain may be a transcriptional inhibitor (i.e., a repressor domain), such as an mSin interaction domain (SID). SID4× domain or a Krüppel-associated box (KRAB) or fragments of the KRAB domain. In some embodiments the effector domain may be an enhancer of transcription (i.e. an activation domain), such as the VP16, VP64 or p65 activation domain. In some embodiments, the nucleic acid binding portion may be linked, for example, with an effector domain that includes but is not limited to a transposase, integrase, recombinase, resolvase, invertase, protease, DNA methyltransferase, DNA demethylase, histone acetylase, histone deacetylase, nuclease, transcriptional repressor, transcriptional activator, transcription factor recruiting, protein nuclear-localization signal or cellular uptake signal. In some embodiments, the effector domain may be a protein domain which exhibits activities which include but are not limited to transposase activity, integrase activity, recombinase activity, resolvase activity, invertase activity, protease activity, DNA methyltransferase activity, DNA demethylase activity, histone acetylase activity, histone deacetylase activity, nuclease activity, nuclear-localization signaling activity, transcriptional repressor activity, transcriptional activator activity, transcription factor recruiting activity, or cellular uptake signaling activity.

Pharmaceutical Compositions

The present disclosure also provides for pharmaceutical compositions comprising the one or more modulating agents. A “pharmaceutical composition” refers to a composition that usually contains an excipient, such as a pharmaceutically acceptable carrier that is conventional in the art and that is suitable for administration to cells or to a subject.

In yet other embodiments, the methods of the disclosure include administering to a subject in need thereof an effective amount (e.g., therapeutically effective amount or prophylactically effective amount) of the treatments provided herein. Such treatment may be supplemented with other known treatments, such as surgery on the subject. In certain embodiments, the surgery is strictureplasty, resection (e.g., bowel resection, colon resection), colectomy, surgery for abscesses and fistulas, proctocolectomy, restorative proctocolectomy, vaginal surgery, cataract surgery, or a combination thereof.

The term “pharmaceutically acceptable” as used throughout this specification is consistent with the art and means compatible with the other ingredients of a pharmaceutical composition and not deleterious to the recipient thereof.

As used herein, “carrier” or “excipient” includes any and all solvents, diluents, buffers (such as, e.g., neutral buffered saline or phosphate buffered saline), solubilisers, colloids, dispersion media, vehicles, fillers, chelating agents (such as, e.g., EDTA or glutathione), amino acids (such as, e.g., glycine), proteins, disintegrants, binders, lubricants, wetting agents, emulsifiers, sweeteners, colorants, flavourings, aromatisers, thickeners, agents for achieving a depot effect, coatings, antifungal agents, preservatives, stabilisers, antioxidants, tonicity controlling agents, absorption delaying agents, and the like. The use of such media and agents for pharmaceutical active components is well known in the art. Such materials should be non-toxic and should not interfere with the activity of the cells or active components.

The precise nature of the carrier or excipient or other material will depend on the route of administration. For example, the composition may be in the form of a parenterally acceptable aqueous solution, which is pyrogen-free and has suitable pH, isotonicity and stability. For general principles in medicinal formulation, the reader is referred to Cell Therapy: Stem Cell Transplantation, Gene Therapy, and Cellular Immunotherapy, by G. Morstyn & W. Sheridan eds., Cambridge University Press, 1996; and Hematopoietic Stem Cell Therapy, E. D. Ball, J. Lister & P. Law, Churchill Livingstone, 2000.

The pharmaceutical composition can be applied parenterally, rectally, orally or topically. Preferably, the pharmaceutical composition may be used for intravenous, intramuscular, subcutaneous, peritoneal, peridural, rectal, nasal, pulmonary, mucosal, or oral application. In a preferred embodiment, the pharmaceutical composition according to the invention is intended to be used as an infuse. The skilled person will understand that compositions which are to be administered orally or topically will usually not comprise cells, although it may be envisioned for oral compositions to also comprise cells, for example when gastro-intestinal tract indications are treated. Each of the cells or active components (e.g., modulants, immunomodulants, antigens) as discussed herein may be administered by the same route or may be administered by a different route. By means of example, and without limitation, cells may be administered parenterally and other active components may be administered orally.

Liquid pharmaceutical compositions may generally include a liquid carrier such as water or a pharmaceutically acceptable aqueous solution. For example, physiological saline solution, tissue or cell culture media, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol may be included.

The composition may include one or more cell protective molecules, cell regenerative molecules, growth factors, anti-apoptotic factors or factors that regulate gene expression in the cells. Such substances may render the cells independent of their environment.

Such pharmaceutical compositions may contain further components ensuring the viability of the cells therein. For example, the compositions may comprise a suitable buffer system (e.g., phosphate or carbonate buffer system) to achieve desirable pH, more usually near neutral pH, and may comprise sufficient salt to ensure isoosmotic conditions for the cells to prevent osmotic stress. For example, suitable solution for these purposes may be phosphate-buffered saline (PBS), sodium chloride solution, Ringer's Injection or Lactated Ringer's Injection, as known in the art. Further, the composition may comprise a carrier protein, e.g., albumin (e.g., bovine or human albumin), which may increase the viability of the cells.

Further suitably pharmaceutically acceptable carriers or additives are well known to those skilled in the art and for instance may be selected from proteins such as collagen or gelatine, carbohydrates such as starch, polysaccharides, sugars (dextrose, glucose and sucrose), cellulose derivatives like sodium or calcium carboxymethylcellulose, hydroxypropyl cellulose or hydroxypropylmethyl cellulose, pregeletanized starches, pectin agar, carrageenan, clays, hydrophilic gums (acacia gum, guar gum, arabic gum and xanthan gum), alginic acid, alginates, hyaluronic acid, polyglycolic and polylactic acid, dextran, pectins, synthetic polymers such as water-soluble acrylic polymer or polyvinylpyrrolidone, proteoglycans, calcium phosphate and the like.

If desired, cell preparation can be administered on a support, scaffold, matrix or material to provide improved tissue regeneration. For example, the material can be a granular ceramic, or a biopolymer such as gelatine, collagen, or fibrinogen. Porous matrices can be synthesized according to standard techniques (e.g., Mikos et al., Biomaterials 14: 323, 1993; Mikos et al., Polymer 35:1068, 1994; Cook et al., J. Biomed. Mater. Res. 35:513, 1997). Such support, scaffold, matrix or material may be biodegradable or non-biodegradable. Hence, the cells may be transferred to and/or cultured on suitable substrate, such as porous or non-porous substrate, to provide for implants.

The pharmaceutical compositions may comprise one or more pharmaceutically acceptable salts. The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids including inorganic or organic bases and inorganic or organic acids. Salts derived from inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic salts, manganous, potassium, sodium, zinc, and the like. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as arginine, betaine, caffeine, choline, N,N′-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethyl-morpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine, and the like. The term “pharmaceutically acceptable salt” further includes all acceptable salts such as acetate, lactobionate, benzenesulfonate, laurate, benzoate, malate, bicarbonate, maleate, bisulfate, mandelate, bitartrate, mesylate, borate, methylbromide, bromide, methylnitrate, calcium edetate, methyl sulfate, camsylate, mucate, carbonate, napsylate, chloride, nitrate, clavulanate, N-methylglucamine, citrate, ammonium salt, dihydrochloride, oleate, edetate, oxalate, edisylate, pamoate (embonate), estolate, palmitate, esylate, pantothenate, fumarate, phosphate/diphosphate, gluceptate, polygalacturonate, gluconate, salicylate, glutamate, stearate, glycollylarsanilate, sulfate, hexylresorcinate, subacetate, hydrabamine, succinate, hydrobromide, tannate, hydrochloride, tartrate, hydroxynaphthoate, teoclate, iodide, tosylate, isothionate, triethiodide, lactate, panoate, valerate, and the like which can be used as a dosage form for modifying the solubility or hydrolysis characteristics or can be used in sustained release or pro-drug formulations. It will be understood that, as used herein, references to specific agents (e.g., neuromedin U receptor agonists or antagonists), also include the pharmaceutically acceptable salts thereof.

Methods of administrating the pharmacological compositions, including agents, cells, agonists, antagonists, antibodies or fragments thereof, to an individual include, but are not limited to, intradermal, intrathecal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, by inhalation, and oral routes. The compositions can be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (for example, oral mucosa, rectal and intestinal mucosa, and the like), ocular, and the like and can be administered together with other biologically-active agents. Administration can be systemic or local. In addition, it may be advantageous to administer the composition into the central nervous system by any suitable route, including intraventricular and intrathecal injection. Pulmonary administration may also be employed by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. It may also be desirable to administer the agent locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion during surgery, topical application, by injection, by means of a catheter, by means of a suppository, or by means of an implant.

Therapy or treatment according to the invention may be performed alone or in conjunction with another therapy, and may be provided at home, the doctor's office, a clinic, a hospital's outpatient department, or a hospital. Treatment generally begins at a hospital so that the doctor can observe the therapy's effects closely and make any adjustments that are needed. The duration of the therapy depends on the age and condition of the patient, the stage of the cancer, and how the patient responds to the treatment. Additionally, a person having a greater risk of developing an inflammatory response (e.g., a person who is genetically predisposed or predisposed to allergies or a person having a disease characterized by episodes of inflammation) may receive prophylactic treatment to inhibit or delay symptoms of the disease.

Delivery of Modulating Agents and Pharmaceutical Compositions

Various delivery systems are known and can be used to administer the agents and pharmacological compositions including, but not limited to, encapsulation in liposomes, microparticles, microcapsules; minicells; polymers; capsules; tablets; and the like. In one embodiment, the agent may be delivered in a vesicle, in particular a liposome. In a liposome, the agent is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Pat. Nos. 4,837,028 and 4,737,323. In yet another embodiment, the pharmacological compositions can be delivered in a controlled release system including, but not limited to: a delivery pump (See, for example, Saudek, et al., New Engl. J. Med. 321: 574 (1989) and a semi-permeable polymeric material (See, for example, Howard, et al., J. Neurosurg. 71: 105 (1989)). Additionally, the controlled release system can be placed in proximity of the therapeutic target (e.g., a tumor), thus requiring only a fraction of the systemic dose. See, for example, Goodson, In: Medical Applications of Controlled Release, 1984. (CRC Press, Boca Raton, Fla.).

Delivery of Modulating Agents that are Polynucleotides

In cases the modulating agents are polynucleotides, they may be delivered to cell using suitable methods. In some embodiments, the polynucleotides may be packaged in viruses or particles, or conjugated to a vehicle for delivering into cells.

In some embodiments, the methods include packaging the polynucleotides in viruses and transducing cell with the viruses. Transduction or transducing herein refers to the delivery of a polynucleotide molecule to a recipient cell either in vivo or in vitro, by infecting the cells with a virus carrying that polynucleotide molecule. The virus may be a replication-defective viral vector. In some examples, the viruses may be virus (e.g. retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses (AAVs)).

In some examples, the viruses are lentiviruses. Lentiviruses are complex retroviruses that have the ability to infect and express their genes in both mitotic and post-mitotic cells. Examples of lentiviruses include human immunodeficiency virus (HIV) (e.g., strain 1 and strain 2), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), BLV, EIAV, CEV, and visna virus. Lentiviruses may be used for nondividing or terminally differentiated cells such as neurons, macrophages, hematopoietic stem cells, retinal photoreceptors, and muscle and liver cells, cell types for which previous gene therapy methods could not be used. A vector containing such a lentivirus core (e.g. gag gene) can transduce both dividing and non-dividing cells.

In certain embodiments, the viruses are adeno-associated viruses (AAVs). AAVs are naturally occurring defective viruses that require helper viruses to produce infectious particles (Muzyczka, N., Curr. Topics in Microbiol. Immunol. 158:97 (1992)). It is also one of the few viruses that can integrate its DNA into nondividing cells. Vectors containing as little as 300 base pairs of AAV can be packaged and can integrate, but space for exogenous DNA is limited to about 4.5 kb. In some cases, an AAV vector may include all the sequences necessary for DNA replication, encapsidation, and host-cell integration. The recombinant AAV vector can be transfected into packaging cells which are infected with a helper virus, using any standard technique, including lipofection, electroporation, calcium phosphate precipitation, etc. Appropriate helper viruses include adenoviruses, cytomegaloviruses, vaccinia viruses, or herpes viruses. Once the packaging cells are transfected and infected, they will produce infectious AAV viral particles which contain the polynucleotide construct. These viral particles are then used to transduce eukaryotic cells.

Methods of non-viral delivery of nucleic acids include lipofection, nucleofection, microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycation or lipid:nucleic acid conjugates, naked DNA, artificial virions, and agent-enhanced uptake of DNA. Lipofection is described in e.g., U.S. Pat. Nos. 5,049,386, 4,946,787; and 4,897,355) and lipofection reagents are sold commercially (e.g., Transfectam™ and Lipofectin™). Cationic and neutral lipids that are suitable for efficient receptor-recognition lipofection of polynucleotides include those of Felgner, WO 91/17424; WO 91/16024. Delivery can be to cells (e.g. in vitro or ex vivo administration) or target tissues (e.g. in vivo administration). Physical methods of introducing polynucleotides may also used. Examples of such methods include injection of a solution containing the polynucleotides, bombardment by particles covered by the polynucleotides, soaking a cell, tissue sample or organism in a solution of the polynucleotides, or electroporation of cell membranes in the presence of the polynucleotides.

Examples of delivery methods and vehicles include viruses, nanoparticles, exosomes, nanoclews, liposomes, lipids (e.g., LNPs), supercharged proteins, cell permeabilizing peptides, and implantable devices. The nucleic acids, proteins and other molecules, as well as cells described herein may be delivered to cells, tissues, organs, or subjects using methods described in paragraphs [00117] to [00278] of Feng Zhang et al., (WO2016106236A1), which is incorporated by reference herein in its entirety.

In some cases, the methods include delivering the barcode construct and/or another element (e.g., a perturbation element) to cells. In such cases, the barcode construct and/or another element (e.g., a perturbation element) may be RNA molecules.

Organs and Tissues

As used herein, “organ” means a collection of tissues joined into structural unit to serve a common function. Examples of organs include, but are not limited to, skin, sweat glands, sebaceous glands, mammary glands, bone, brain, hypothalamus, pituitary gland, pineal body, heart, blood vessels, larynx, trachea, bronchus, lung, lymphatic vessel, salivary glands, mucous glands, esophagus, stomach, gallbladder, liver, pancreas, small intestine, large intestine, colon, urethra, kidney, adrenal gland, conduit, ureter, bladder, fallopian tube, uterus, ovaries, testes, prostate, thyroid, parathyroid, meibomian gland, parotid gland, tonsil, adenoid, thymus, and spleen. In one example, the organ is liver. In certain examples, the organ is liver, spleen, intestine, colon, bone marrow, an immune tissue or organ, or a tissue or organ of the gastrointestinal track. In certain cases, the organ or tissue is an organ or tissue of the immune system, e.g., lymphoid organs such as bone marrow, thymus, lymph nodes, spleen, tonsils, other specialized tissues in the mucous membranes of the body, e.g., the bowel. In certain cases, the organ or tissue is a part of the gastrointestinal track, e.g., pharynx, esophagus, stomach, duodenum, small intestine, large intestine.

As used herein, “tissue” means an aggregate of cells. Examples of tissues include, but are not limited to, connective tissue (e.g., areolar connective tissue, dense connective tissue, elastic tissue, reticular connective tissue, and adipose tissue), muscle tissue (e.g., skeletal muscle, smooth muscle and cardiac muscle), genitourinary tissue, gastrointestinal tissue, pulmonary tissue, bone tissue, nervous tissue, and epithelial tissue (e.g., simple epithelium and stratified epithelium), endoderm-derived tissue, mesoderm-derived tissue, and ectoderm-derived tissue.

As used herein, the one or more genes may be involved in functions, growth, proliferation, and generation of stem cells. As used herein, “stem cell” means a cell that exhibits potency and self-renewal. Stem cells include, but are not limited to, totipotent cells, pluripotent cells, multipotent cells, oligopotent cells, unipotent cells, and progenitor cells. Stem cells may be embryonic stem cells, peri-natal stem cells, adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Injuries and Diseases

The methods herein may be used for treating various injuries and diseases, e.g., an acute injury, a chronic injury, injury is caused by an metabolic insult (e.g., high fat diet), a chronic disease, or a liver disease.

The injury herein may be an acute injury. As used herein, the term “acute injury” includes injuries that have occurred suddenly or recently occurred. For example, an acute injury may have occurred suddenly, e.g., due to a traumatic event (external or internal), infections (e.g., caused by bacterial viruses, fungi and parasites), stroke (cerebral circulatory disturbance and intracerebral or subarachnoid haemorrhage), intoxications, and traumatic lesions. The injury herein may be a chronic injury or disease. As used herein, the term “chronic injury” an injury disease that has a slow, insidious onset and generally a long duration.

The methods herein may be used for treating various diseases. In some cases, the disease is metabolic diseases such as obesity, as well as related disorders such as eating disorder, cachexia, diabetes mellitus, hypertension, coronary heart disease, hypercholesterolemia, dyslipidemia, osteoarthritis, gallstones, and sleep apnea, and disorders related to ROS defense, such as diabetes mellitus, neurodegenerative disorders, and cancer, e.g. cancers of the reproductive organs, high blood pressure, hypertension, high blood cholesterol, dyslipidemia, type 2 diabetes, insulin resistance, glucose intolerance, hyperinsulinemia, coronary heart disease, angina pectoris, congestive heart failure, stroke, gallstones, cholecystitis and cholelithiasis, gout, osteoarthritis, obstructive sleep apnea and respiratory problems, some types of cancer (such as endometrial, breast, prostate, and colon), complications of pregnancy, poor female reproductive health (such as menstrual irregularities, infertility, irregular ovulation), bladder control problems (such as stress incontinence); uric acid nephrolithiasis; psychological disorders.

In some examples, the injury or disease is a liver injury or disease. Examples of liver injuries or disease include nonalcoholic steatohepatitis, alcoholic hepatitis, and Reye's Syndrome, liver disorders or injuries caused by trauma, intoxication, in particular by alcohol, drugs or food intoxication, radiation, infection, cholestasis, immune reactions, inherited liver diseases and inherited metabolic liver diseases, cirrhosis, alcoholic and nonalcoholic liver disease, chronic hepatitis, Wilson's Disease, and heamochromatosis, liver diseases caused by alcohol (e.g. ASH), non-alcoholic fatty liver changes (such as NAFLD including NASH), nutrition-mediated liver injury (for example starvation), other toxic liver injury (such as unspecific hepatitis induced by e.g. drugs such as but not limited to acetaminophen (paracetamol), chlorinated hydrocarbons (e.g. CCl4), amiodarone (cordarone), valproate, tetracycline (only i.v.), isoniacid, or food intoxication resulting in acute or chronic liver failure, e.g. by consumption of mushrooms containing aflatoxins or ingestion of certain metal (such as copper or cadmium) or herbal products used in natural medicine (homeopatics such as Milk thistle, Chaparral, Kawa-Kawa), interference of bilirubin metabolism, hepatitis like syndromes, cholestasis, granulomatous lesions, intrahepatic vascular lesions and cirrhosis), trauma and surgery (e.g. Pringle maneuver), radiation-mediated liver injury (such as caused by radiotherapy), inflammatory liver disease [caused e.g. by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections] and autoimmune-mediated liver disease (e.g. autoimmune hepatitis), injury due to sepsis, genetic liver disorders (such as heamochromatosis and alpha1 antitrypsin deficiency), and other inherited metabolic liver diseases, e.g. metabolic steatohepatitis (MSH).

Liver diseases or injuries may also encompass liver cancer. The term “liver cancer” within the meaning of the invention includes carcinomas in the liver, hepatocellular carcinoma (HCC), metastases in liver originated from any organ (e.g. colon, breast), cholangiocarcinoma, in which epithelial cell components of the tissue are transformed resulting in a malignant tumor, subtypes of the mentioned disorders, e.g., liver cancers characterized by intracellular proteinaceous inclusion bodies, HCCs characterized by hepatocyte steatosis, and fibrolamellar HCC. For example, precancerous lesions are also included such as those characterized by increased hepatocyte cell size (the “large cell” change), and those characterized by decreased hepatocyte cell size (the “small cell” change) as well as macro regenerative (hyperplastic) nodules. Liver disease is further understood to comprise hyperproliferative diseases of liver e.g. benign liver neoplasms such as liver cell adenoma and/or focular nodular hyperplasia (FNH).

In some embodiments, the diseases also include cancers. Examples of cancers include liquid tumors such as leukemia (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (e.g., Hodgkin's disease, non-Hodgkin's disease), Waldenstrom's macroglobulinemia, heavy chain disease, or multiple myeloma, solid tumors such as sarcomas and carcinomas. Examples of solid tumors include, but are not limited to fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, epithelial carcinoma, bronchogenic carcinoma, hepatoma, colorectal cancer (e.g., colon cancer, rectal cancer), anal cancer, pancreatic cancer (e.g., pancreatic adenocarcinoma, islet cell carcinoma, neuroendocrine tumors), breast cancer (e.g., ductal carcinoma, lobular carcinoma, inflammatory breast cancer, clear cell carcinoma, mucinous carcinoma), ovarian carcinoma (e.g., ovarian epithelial carcinoma or surface epithelial-stromal tumour including serous tumour, endometrioid tumor and mucinous cystadenocarcinoma, sex-cord-stromal tumor), prostate cancer, liver and bile duct carcinoma (e.g., hepatocelluar carcinoma, cholangiocarcinoma, hemangioma), choriocarcinoma, seminoma, embryonal carcinoma, kidney cancer (e.g., renal cell carcinoma, clear cell carcinoma, Wilm's tumor, nephroblastoma), cervical cancer, uterine cancer (e.g., endometrial adenocarcinoma, uterine papillary serous carcinoma, uterine clear-cell carcinoma, uterine sarcomas and leiomyosarcomas, mixed mullerian tumors), testicular cancer, germ cell tumor, lung cancer (e.g., lung adenocarcinoma, squamous cell carcinoma, large cell carcinoma, bronchioloalveolar carcinoma, non-small-cell carcinoma, small cell carcinoma, mesothelioma), bladder carcinoma, signet ring cell carcinoma, cancer of the head and neck (e.g., squamous cell carcinomas), esophageal carcinoma (e.g., esophageal adenocarcinoma), tumors of the brain (e.g., glioma, glioblastoma, medulloblastoma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, schwannoma, meningioma), neuroblastoma, retinoblastoma, neuroendocrine tumor, melanoma, cancer of the stomach (e.g., stomach adenocarcinoma, gastrointestinal stromal tumor), or carcinoids. Lymphoproliferative disorders are also considered to be proliferative diseases, cancers in which expression of an EMT program e.g., breast cancer, colon cancer, lung cancer, prostate cancer, testicular cancer, brain cancer, skin cancer, rectal cancer, gastric cancer, esophageal cancer, tracheal cancer, head and neck cancer, pancreatic cancer, liver cancer, ovarian cancer, lymphoid cancer, cervical cancer, vulvar cancer, melanoma, mesothelioma, renal cancer, bladder cancer, thyroid cancer, bone cancers, carcinomas, sarcomas, and soft tissue cancers.

Methods of Identifying Target Genes

The present disclosure also includes identifying genes that can be used as target for treating the injuries and diseases. In general, the method include determining expression of one or more genes from single cells in an organ at a first time point and a second time point; selecting a first subset of genes from the one or more genes, wherein expression of the first subset of genes at the first and the second time points are different; determining spatial locations of cells expressing the first subset of genes in the organ at the first and the second time points by an in situ hybridization assay; and selecting a second subset of genes based on the spatial locations of the cells expressing the second subset of genes.

Gene Profiling in Single Cells

In some embodiments, the methods herein include determining expression of one or more genes from single cells in an organ over a time course. In some cases, the expression of the gene(s) at a first time point and a second time point may be determined and compared. Subject of genes whose expressions alters at different time points may be selected. In some examples, the time points may be two or more of: a time point before the injury, a time point in an injury phase, a time point in a recovery phase, a time point in a proliferative phase, and a time in a termination phase.

In some examples, the expression of the gene(s) may be determined by single cell gene expression profiling. In certain examples, such methods may include separating, detecting and/or quantifying markers at the nucleic acid level, more particularly RNA level, e.g., at the level of hnRNA, pre-mRNA, mRNA, or cDNA. Standard quantitative RNA or cDNA measurement tools known in the art may be used. Non-limiting examples include hybridisation-based analysis, microarray expression analysis, digital gene expression profiling (DGE), RNA-in-situ hybridisation (RISH), Northern-blot analysis and the like; PCR, RT-PCR, RT-qPCR, end-point PCR, digital PCR or the like; supported oligonucleotide detection, pyrosequencing, polony cyclic sequencing by synthesis, simultaneous bi-directional sequencing, single-molecule sequencing, single molecule real time sequencing, true single molecule sequencing, hybridization-assisted nanopore sequencing, sequencing by synthesis, single-cell RNA sequencing (sc-RNA seq), or the like. By means of an example, methods to profile the RNA content of large numbers of individual cells have been recently developed. To do so, special microfluidic devices have been developed to encapsulate each cell in an individual drop, associate the RNA of each cell with a ‘cell barcode’ unique to that cell/drop, measure the expression level of each RNA with sequencing, and then use the cell barcodes to determine which cell each RNA molecule came from.

In certain embodiments, the invention involves plate based single cell RNA sequencing (see, e.g., Picelli, S. et al., 2014, “Full-length RNA-seq from single cells using Smart-seq2” Nature protocols 9, 171-181, doi:10.1038/nprot.2014.006).

In certain embodiments, the invention involves high-throughput single-cell RNA-seq and/or targeted nucleic acid profiling (for example, sequencing, quantitative reverse transcription polymerase chain reaction, and the like) where the RNAs from different cells are tagged individually, allowing a single library to be created while retaining the cell identity of each read. In this regard reference is made to Macosko et al., 2015, “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets” Cell 161, 1202-1214; International patent application number PCT/US2015/049178, published as WO2016/040476 on Mar. 17, 2016; Klein et al., 2015, “Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells” Cell 161, 1187-1201; International patent application number PCT/US2016/027734, published as WO2016168584A1 on Oct. 20, 2016; Zheng, et al., 2016, “Haplotyping germline and cancer genomes with high-throughput linked-read sequencing” Nature Biotechnology 34, 303-311; Zheng, et al., 2017, “Massively parallel digital transcriptional profiling of single cells” Nat. Commun. 8, 14049 doi: 10.1038/ncomms14049; International patent publication number WO2014210353A2; Zilionis, et al., 2017, “Single-cell barcoding and sequencing using droplet microfluidics” Nat Protoc. January; 12(1):44-73; Cao et al., 2017, “Comprehensive single cell transcriptional profiling of a multicellular organism by combinatorial indexing” bioRxiv preprint first posted online Feb. 2, 2017, doi: dx.doi.org/10.1101/104844; Rosenberg et al., 2017, “Scaling single cell transcriptomics through split pool barcoding” bioRxiv preprint first posted online Feb. 2, 2017, doi: dx.doi.org/10.1101/105163; Vitak, et al., “Sequencing thousands of single-cell genomes with combinatorial indexing” Nature Methods, 14(3):302-308, 2017; Cao, et al., Comprehensive single-cell transcriptional profiling of a multicellular organism. Science, 357(6352):661-667, 2017; and Gierahn et al., “Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput” Nature Methods 14, 395-398 (2017), all the contents and disclosure of each of which are herein incorporated by reference in their entirety.

In certain embodiments, the invention involves single nucleus RNA sequencing. In this regard reference is made to Swiech et al., 2014, “In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9” Nature Biotechnology Vol. 33, pp. 102-106; Habib et al., 2016, “Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons” Science, Vol. 353, Issue 6302, pp. 925-928; Habib et al., 2017, “Massively parallel single-nucleus RNA-seq with DroNc-seq” Nat Methods. 2017 October; 14(10):955-958; and International patent application number PCT/US2016/059239, published as WO2017164936 on Sep. 28, 2017, which are herein incorporated by reference in their entirety.

As discussed, while the platform has been optimized for the generation of individually barcoded single-cell sequencing libraries following confinement of cells and mRNA capture beads (Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., Trombetta, J. J., Weitz, D. A., Sanes, J. A., Shalek, A. K., Regev, A., McCarroll, S. A. “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets” Cell, 161, 1202-1214), it is capable of multiple levels of data acquisition. The platform is compatible with other assays and measurements performed with the same array. For example, profiling of human antibody responses by integrated single-cell analysis is discussed with regard to measuring levels of cell surface proteins (Ogunniyi, A. O., B. A. Thomas, T. J. Politano, N. Varadarajan, E. Landais, P. Poignard, B. D. Walker, D. S. Kwon, and J. C. Love, “Profiling Human Antibody Responses by Integrated Single-Cell Analysis” Vaccine, 32(24), 2866-2873.) The authors demonstrate a complete characterization of the antigen-specific B cells induced during infections or following vaccination, which enables and informs one of skill in the art how interventions shape protective humoral responses. Specifically, this disclosure combines single-cell profiling with on-chip image cytometry, microengraving, and single-cell RT-PCR.

Seq-Well

In some embodiments, the expression of the one or more genes may be determined using a method comprising a first functionalized surface of each well or container, wherein the functionalized surface comprises an affinity resin; and a second functionalized surface, such as a top surface of an array material, wherein the functionalized surface provides accessible ionic functional groups. The second surface is configured to be sealed, for example with a permeable membrane, as described herein. According to the invention, the well or container is loaded with one or more cells, such as 1, 2, 3, 4, 5 or more cells of a cell or tissue sample, together with a detection agent, and sealed, for example with a permeable membrane as described herein. In an embodiment of the invention, the detection agent is attached to a barcoded bead. In an embodiment of the invention, the detection reagent is selected to bind to a peptide or nucleic acid. In certain example embodiments, additional reagents may be preloaded into the well or container before sealing. Such reagents can include, without limitation, DNA and/or RNA amplification reagents, polymerases, reverse transcriptase, nucleases, enzymes, antigen binding proteins, labeling reagents, and the like.

In one embodiment, the diagnostic is configured to detect one or more mutated nucleic acids, for example by amplification based methods and/or sequencing. For example, reverse transcription PCR (RT-PCR) can be used to detect mutations in transcribed genes. Additionally, any sequencing technique can be used to determine the presence of a mutation. The present invention also provides for a kit that includes primers that are specific to sequences encompassing the mutations.

In some examples, the method include Seq-Well. An example of the Seq-Well approach is described in Gierahn et al., Nature Methods 2017. In some examples, Seq-Well assays may be performed as described in PCT/US2018/057170, incorporated herein by reference.

Membrane Preparation: (1.) Place a pre-cut (22×66 mm) polycarbonate membrane onto a glass slide, carefully using a gloved finger and tweezers to separate the membrane and paper (Note 1: orientation of polycarbonate membranes not important; discard any membranes that have creases or large-scale imperfections). (2.) Place membranes onto a shelf in the plasma cleaner (Note: Place membranes on bottom shelf to reduce risk of them flying after vacuum is removed. (3) Close the plasma cleaner door, and then turn on the main power and pump switch. To form a vacuum, ensure that the 3-way valve lever is at the 9:00 position as shown below. (4.) Allow vacuum to form for 2 minutes. Once the vacuum has formed, simultaneously turn the valve to 12:00 while turning the power to the Hi setting (shown below). Note: plasma (pink) form should be observed. (Note: The plasma should be a bright pink. If not, adjust the air valve to increase or decrease the amount of oxygen you are letting into the chamber.) (5) Treat membranes with plasma for 7 minutes. (6) Critical—After treatment, in the following order, turn the RF level valve from HIGH to OFF, then turn off the power followed by turning off the vacuum. Then slowly open the valve until you can barely hear air entering chamber (Approximate valve position shown below). Leave until door opens (˜5 min). (7.) Remove slides from plasma cleaner and transfer to a 4 well plate. (Note 1: if membranes have slightly folded over, Slowly flip the membrane back using needle nosed tweezers; Note 2: if membranes have blown off the slide entirely, repeat above procedure to ensure you know which side was exposed to plasma.) (8.) Quickly pipet 5 mL of 1×PBS over the dry membrane, preventing the membrane from folding on itself (Note: gently hydrate one end of the membrane with a single drop so that it adheres to the slide before dispensing the entire volume) (9.) Remove any air bubbles underneath the membrane using wafer forceps. (10.)

Membranes are now functionalized and ready for use. (Note 1: membranes solvated with 1×PBS should be used same day; Note 2: if transporting solvated membranes (e.g. between buildings), remove all by ˜1 mL of PBS to prevent membranes from flipping within the dish; note 3: Alternatively, membranes can be solvated in a 2% Ficoll solution and stored dry for 2 weeks at room temperature.) When ready to use membranes, can be rehydrated with 1×PBS.

Bead Loading: (1.) Aspirate storage solution and solvate arrays with 5 mL of bead loading buffer (BLB). (2.) Place arrays under vacuum with rotation (50 rpm) for 10-15 minutes to remove air bubbles in wells. (3.) Aliquot 110,000 beads from stock into a 1.5 mL tube and spin on a tabletop centrifuge for 10-15 seconds to form a pellet. (4.) Aspirate storage buffer and wash beads once in 500 μL of BLB. (5.) Pellet beads, aspirate BLB, and resuspend beads in 200 μL of BLB. (Note: for each array, recommended to load ˜110,000 beads, e.g., when running two arrays you would aliquot 220,000 beads, wash, and re-suspend in 400 μL of BLB.) (6.) Before loading beads, thoroughly aspirate BLB from the dish containing the array, being careful not to aspirate or dry the PDMS surface of the array. (7.) Use a 200 μL pipette to apply 200 μL containing 110,000 beads, in a drop-wise fashion, to the surface of the array. (8.) Place the loaded array(s) onto a rotator for 10 minutes (75 rpm). (9.) Thoroughly wash arrays to remove excess beads from the surface. For each wash: (a.) Position the array so that it sits in the center of the 4-well dish. (b.)

Dispense 500 μL of BLB in the upper right corner of the array and 500 μL in the bottom right corner of the array (careful not to directly pipette onto the microwells, as it can dislodge beads). (c.) Using wafer forceps, push the array against the left side of the 4-well dish to create a capillary flow, which will help remove beads from the surface. (d.) Aspirate the liquid, reposition the array, and repeat on the opposite side. (10.) Repeat step 9 as necessary. Periodically examine the array under microscope to verify that no loose beads are present on the surface, as this will interfere with membrane attachment. (11.) Once excess beads have been removed from the surface, solvate the array with 5 mL of BLB and proceed to cell loading. (Notes: If continuing to cell loading immediately (i.e., within 1-5 hours), loaded arrays should be stored in 5 mL of BLB. Loaded arrays can be stored for up to 72 hours in Array Quenching Buffer.

Cell Loading (without imaging): (1) Arrays should be loaded with beads and immersed in BLB. (2) Obtain a cell or tissue sample and prepare a single cell suspension using your preferred protocol (3) While preparing your single cell suspension, aspirate the BLB from array and soak it in 5 mL of RPMI+10% FBS for 5 minutes (4) After obtaining a single cell suspension, count cells using a hemocytometer and make a new solution of 10,000 cells in 200 μL of RPMI+10% FBS (Cell Loading Solution) (5) Aspirate the RPMI+10% FBS solution, center the array in well, then load the cell loading solution in a dropwise fashion onto the surface of the array (6) Intermittently rock the array in the x & y direction for 5 minutes (to visualize membrane sealing or cell loading, pre-label cells with AF647-anti CD45 if leukocytes or another surface marker in AF647) (7) Wash arrays 4× with 5 mL of PBS to remove FBS in media—this is critical to ensure successful membrane attachment (Aspirate final PBS wash and replace with 5 mL of RPMI media (no FBS).

Cell Loading (with imaging): (1) When pre-imaging cells, cells should be loaded first as beads will obstruct view of many cells and bead autofluorescence can interfere with the signal (2) Obtain a cell or tissue sample and prepare a single cell suspension using your preferred protocol (3) Count cells using a hemocytometer and resuspend 10,000 cells in 200 μL of cold CellCover (Anacyte). (4) Incubate cells at 4° C. for 1 hour (5) After the cells have been fixed, perform antibody staining at 4° C. (Note: Some epitopes may no longer be available as a result of the fixation process) (6) Wash cells twice with 1×PBS, resuspend in 200 μL of CellCover10 buffer (pH 10+10% FBS) and place on ice. (7) Obtain empty functionalized array(s), aspirate storage solution and soak array(s) with 5 mL of CellCover10 buffer (8) Aspirate media and load fixed cells onto the array(s) in a dropwise format (9) Gently rock the array(s) in the x & y direction for 5 minutes (10) Wash array(s) twice with 5 mL of CellCover10 (pH 10+10% FBS), then solvate in 5 mL of CellCover (No FBS). (11) Place a lift slip onto the array(s), then image with a microscope (12) After imaging, wash array(s) in 5 mL of CellCover10 media (13) Immediately load beads using the bead loading protocol provided above (14) Proceed with membrane sealing.

Membrane Sealing: (1) Use wafer forceps to transfer the array(s) from media to the lid of a 4-well dish, being careful to keep the array as close to horizontal as possible (2) Use wafer forceps to remove a pre-treated membrane from the 4-well dish. (3) Gently dab away moisture from the glass slide on the paper towel until the membrane does not spontaneously change position on the glass slide (4) Carefully position the membrane on the center of the microscope slide, leaving a small (2-3 mm) membrane overhang beyond the edge of slide (5) Holding the membrane in your left hand, invert the microscope slide so that the treated surface is facing down (6) Place the overhang of the membrane in contact with the PDMS surface of the array just above the boundary of the microwells (7) Using your right hand, firmly hold down the overhang of the membrane against the PDMS surface of the array (8) Note: While maintaining pressure with your right hand to hold the membrane in place, gently apply the membrane; for optimal results, use little to no pressure while applying the membrane with the left hand; Attempts to manually seal the microwell device using pressure result in a ‘squeegee’ effect, effectively removing moisture from the membrane while fixing membrane creases in place). (9) After applying the membrane, carefully pry the array and membrane from the surface of the lid and transfer to an Agilent clamp (10) Tighten clamp to the point of resistance and place in a 37° C. incubator for 30 minutes (11) Repeat membrane sealing procedure if running multiple arrays.

Cell Lysis and Hybridization: (1) Remove the clamp from the incubator, and then remove the array from the Agilent clamp (2) Submerge the array with top slide still attached in 5 mL of pre-lysis buffer (5 M Guanidine thiocyanate and 1 mM EDTA) (3) Gently rock the array in pre-lysis buffer until the top glass slide lifts off (Note: time necessary for detachment of the top slide varies (10 seconds-5 minutes) (4) Once the top slide has detached, aspirate the pre-lysis buffer and add 5 mL of complete lysis buffer to the array (Note: Alternatively, 5 mL of complete lysis buffer can be prepared by adding 25 μL of 20% Sarkosyl and 50 μL of Beta-mercaptoethanol to pre-lysis buffer; use a separate waste container for lysis buffer because guanidine thiocyanate can react with bleach in TC traps to create toxic gas (5) Rock the array for 20 minutes at 50-60 rpm (6) Remove the lysis buffer and wash once with 5 mL of hybridization buffer. (7) Aspirate hybridization buffer and add another 5 mL of hybridization buffer to the array and rock for 40 minutes at 50-60 rpm (8) While array are rocking in hybridization buffer, prepare reverse transcription master mix.

Bead Removal: (1) Aspirate hybridization buffer and replace with 5 mL of wash buffer (2) rock for 3 min (3) remove membrane with fine-tipped tweezers (4) identify orientation of a lifter slip such that feet are facing upwards (5) place lifter slip(s) in a separate 4-well dish with feet oriented upwards (6) carefully transfer the array(s) to the new dish, inverting the array(s) so that the PDMS surface is in contact with the feet of the lift slips (7) transfer 3 mL of wash buffer to the dish containing the inverted array(s) (8) precisely (+/−2 grams) weigh the dish containing inverted array(s) to properly balance the centrifuge (9) Spin for 5 minutes at 1000×G. (10) After centrifugation, collect the beads and transfer them to a 15 mL conical tube for each array, if running multiple: (a) rinse the glass slide on the back of the array with wash buffer (b) invert the array and rinse the PDMS surface (c) lightly scrape the surface of the array to remove any retained beads using a microscope slide (d) remove array and rinse both sides of the lifter slips (e) collect suspended beads (10-12 mL) and transfer to a 15-mL conical tube. (11) Spin conical tube(s) for 5 minutes at 3000×G. (12) aspirate all liquid but 1 mL and transfer beads to a clean 1.5 mL centrifuge tube (13) Rinse 15 mL conical with 500 μL of wash buffer and add to the 1.5 mL tube.

Graph-Based Clustering of Single-Cell Transcriptomes

In some cases, expression data may be analyzed. For single cell-clustering analyses, an example approach is similar to the recently proposed clustering strategy for Drop-Seq data. Briefly, as in Macosko et al. (Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., Trombetta, J. J., Weitz, D. A., Sanes, J. A., Shalek, A. K., Regev, A., McCarroll, S. A. “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets” Cell, 161, 1202-1214. In some examples, first the set of genes that is most variable across the dataset is identified, after controlling for the relationship in single-cell RNA-seq data that inherently exists between mean expression and variability by binning genes into 20 bins based on their average expression level, and z-scoring dispersion (mean/variance) estimates within a bin. Genes which are detected in less than 2.5% of PBMCs (5% of monocytes for the Mtb experiments) are excluded, and a dispersion cutoff of 0.5 is used to select variable genes, resulting in the selection of 687 variable genes across 4,296 PBMCs and 377 variable genes across 4,638 macrophages.

In some cases, reducing the dimensionality of the dataset is performed, e.g., using principal components analysis. As prescribed in Macosko et al. (Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., Trombetta, J. J., Weitz, D. A., Sanes, J. A., Shalek, A. K., Regev, A., McCarroll, S. A. “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets” Cell, 161, 1202-1214), Applicants ran PCA using the prcomp function in R. Applicants then selected PCs for further downstream analysis (11 PCs in PBMC analysis and 5 PCs in TB Analysis). Markers for distinct cell types may be highly represented among the genes with the largest scores along these PCs. Then t-distributed stochastic neighbor embedding (t-SNE) may be performed using cell loadings for the significant principal components as input, to visualize the structure of the data in two dimensions.

For example, graph-based clustering methods may be used, similar to those that have been recently proposed for both single cell RNA-seq and mass cytometry data (Levine, J. H., et al., “Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis” (2015) Cell 162, 184-197 & Xu, C., and Su., Z. “Identification of cell types from single-cell transcriptomes using a novel clustering method” (2015) Bioinformatics 31(12):1974-1980). A Euclidean distance matrix may be generated on the loadings for the significant principal components as described above, and use this to construct a k-nearest neighbor graph (KNN, k=50 in PBMC analysis, k=40 in TB analysis). The goal may be to identify ‘quasi-cliques’ Xu, C., and Su., Z. “Identification of cell types from single-cell transcriptomes using a novel clustering method” (2015) Bioinformatics 31(12):1974-1980), or ‘communities’ (Levine, J. H., et al., “Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis” (2015) Cell 162, 184-197) of cells that were highly interconnected across this graph. First the KNN graph may be converted into a weighted shared nearest neighbor (SNN) graph, where the weight between any two cells is represented by the percent overlap in their respective K-nearest neighborhoods (Jaccard distance), and pruned low-quality edges with a Jaccard distance of <0.1 (less than 10% overlap in local neighborhoods). Finally, to group the cells into clusters, a method for modularity optimization may be used, which aims to optimize a function describing the density of connections within a cluster versus connections between clusters, essentially to identify highly interconnected nodes within the SNN graph. The smart local moving algorithm may be applied, which is similar to the widely used ‘Louvain’ algorithm for community detection, but implements a local moving heuristic that enables communities to be split up and iteratively re-organized in an attempt to improve the overall partition modularity. This grants the SLM algorithm additional freedom in identifying an optimal clustering solution, and increased sensitivity may be empirically observed and this approach may be consistency applied to single cell data.

In Situ Hybridization

The methods may further include determining spatial locations of cells expressing the first subset of genes in the organ at the first and the second time points by an in situ hybridization assay; and selecting a second subset of genes based on the spatial locations of the cells expressing the second subset of genes.

The in situ hybridization assay may be fluorescene in situ hybridization (FISH). FISH may refer to a cytogenetic technique used to detect and localize the presence or absence of specific nucleic acid sequences. FISH uses fluorescent probes that bind target sequences to define patterns of gene expression within cells and tissues. The term “FISH probe molecule” refers to a physical probe molecule having a nucleic acid sequence of the oligonucleotide sequence of the FISH probe molecule consisting of a plurality of the in-situ hybridization, for example by FISH provided oligonucleotide sequences for FISH probe molecules has been selected. Although this probe molecules are called FISH probe molecules, they do not necessarily need with fluorescent, but can also be labeled with non-fluorescent markers, for example with chromophores.

In some examples, the in situ hybridization assay may be single molecule FISH (smFISH). In some embodiments, genes or RNA within the tissue or organ is visualized (thus determined spatial location of cells expressing the genes or RNA) using single-molecule fluorescence in-situ hybridization (smFISH) (see Skinner, S. O., et al. Measuring mRNA copy number in individual Escherichia coli cells using single-molecule fluorescent in situ hybridization. Nat. Protoc. 8, 1100-1113 (2013); Lyubimova, A. et al. Single-molecule mRNA detection and counting in mammalian tissue. Nat. Protoc. 8, 1743-1758 (2013); Lubeck, E. & Cai, L. Single-cell systems biology by super-resolution imaging and combinatorial labeling. Nat. Methods 9, 743-748 (2012); Lubeck, E., et al. Single-cell in situ RNA profiling by sequential hybridization. Nat. Methods 11, 360-361 (2014); Ke, R. et al. In situ sequencing for RNA analysis in preserved tissue and cells. Nat. Methods 10, 857-860 (2013); Levesque, M. J., et al. Visualizing SNVs to quantify allele-specific expression in single cells. Nat. Methods 10, 865-867 (2013); and Levesque, M. J. & Raj, A. Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation. Nat. Methods 10, 246-248 (2013)). Description of single molecule FISH can also be found in, for example, Raj A., et al., 2008, “Imaging individual mRNA molecules using multiple singly labeled probes,” Nature Methods 5(10): 877-879; Femino A., et al., 1998, “Visualization of single RNA transcripts in situ,” Science 280: 585-590; Vargas D., et al., 2005, “Mechanism of mRNA transport in the nucleus,” Proc. Natl. Acad. Sci. of USA 102: 17008-17013; Raj A., et al., 2006, “Stochastic mRNA synthesis in mammalian cells,” PLoS Biology 4(10):e309; Maamar H., et al., 2007, “Noise in gene expression determines cell fate in B. subtilis,” Science, 317: 526-529; and Raj A., et al., 2010 “Variability in gene expression underlies incomplete penetrance,” Nature463:913; each of which (including any Supplemental Material) is hereby incorporated by reference herein in its entirety.

In some cases, microscopy technology is used for obtaining and analyzing images obtained from in situ hybridization. For example, super-resolution microscopy is used to visualize one or more labeled transcripts within tissues or organs. Exemplary super-resolution technologies include but are not limited to I⁵M microscopy, 4Pi-microscopy, Stimulated Emission Depletion microscopy (STEDM), Ground State Depletion microscopy (GSDM), Spatially Structured Illumination microscopy (SSIM), Photo-Activated Localization Microscopy (PALM), Reversible Saturable Optically Linear Fluorescent Transition (RESOLFT), Total Internal Reflection Fluorescence Microscope (TIRFM), Fluorescence-PALM (FPALM), Stochastical Optical Reconstruction Microscopy (STORM), Fluorescence Imaging with One-Nanometer Accuracy (FIONA), and combinations thereof. Descriptions of relevant techniques can be found in Chi, 2009 “Super-resolution microscopy: breaking the limits, Nature Methods 6(1):15-18; Blow 2008, “New ways to see a smaller world,” Nature 456:825-828; Hell, et al., 2007, “Far-Field Optical Nanoscopy,” Science 316: 1153; R. Heintzmann and G. Ficz, 2006, “Breaking the resolution limit in light microscopy,” Briefings in Functional Genomics and Proteomics 5(4):289-301; Garini et al., 2005, “From micro to nano: recent advances in high-resolution microscopy,” Current Opinion in Biotechnology 16:3-12; Bewersdorf et al., 2006, “Comparison of I⁵M and 4Pi-microscopy,” 222(2):105-117; and Wells, 2004, “Man the Nanoscopes,” JCB 164(3):337-340; each of which (including Supplemental Material) is hereby incorporated by reference herein in its entirety. In some embodiments, light sheet microscopy (as described in greater detail in the examples set forth herein) is used to visualize one or more labeled (according to any method described herein) or unlabeled aspect of the tissue or its molecular constituents.

The present application also provides aspects and embodiments as set forth in the following numbered Statements:

Statement 1. A method of treating an injury in an organ or tissue, comprising administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes or gene products that have functions in regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof.

Statement 2, An agent that modulates expression and/or activity of one or more genes or gene products that have functions in regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof, for use in a method of treating an injury in an organ or tissue.

Statement 3. Use of an agent that modulates expression and/or activity of one or more genes or gene products that have functions in regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof, for the manufacture of a medicament for use in a method of treating an injury in an organ or tissue.

Statement 4. The method of Statement 1, or the agent for use according to Statement 2, or the use according to Statement 3, wherein the method further comprises administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in PPAR signaling pathway, complement and coagulation cascades, PPARa activated gene expression, biological oxidations, metabolism of lipids and lipoproteins, nasopharyngeal carcinoma, intestine probiotics, plasma cell vs plasmablast, liver cancer, liver specific genes, multiple myeloma, response to UVb radiation, heart atrium vs ventricle, aging kidney no blood, endocrine therapy resistance, liver cancer, breast cancer basal, foxa2 targets, stem cell, lung cancer kras, tlx targets, liver cancer subclass g123, liver cancer subclass proliferation, liver cancer stem cell, liver cancer recurrence, liver cancer subclass s3, hepatoblastoma, liver development, liver hnf1a targets, matrisome, liver cancer krt19, fatty acid catabolic process, ammonium ion metabolic process, protein activation cascade, regulation of wound healing, response to estradiol, response to acid chemical, sterol homeostasis, lipoprotein metabolic process, fatty acid beta oxidation, protein maturation, regulation of locomotion, organic hydroxy compound metabolic process, organic acid biosynthetic process, monocarboxylic acid metabolic process, response to inorganic substance, regulation of vesicle mediated transport, regulation of fatty acid metabolic process, organic hydroxy compound transport, defense response, organophosphate ester transport, lipid homeostasis, secretion, anion transport, regulation of lipid biosynthetic process, response to xenobiotic stimulus, regulation of response to external stimulus, small molecule biosynthetic process, regulation of response to external stimulus, regulation of lipid metabolic process, amine metabolic process, autophagy, regulation of secretion, apoptotic signaling pathway, acute inflammatory response, regulation of catabolic process, maintenance of location, regulation of protein secretion, organic acid metabolic process, response to oxygen levels, regulation of cellular ketone metabolic process, organic acid catabolic process, regulation of response to wounding, regulation of extrinsic apoptotic signaling pathway, cellular lipid catabolic process, regulation of reactive oxygen species metabolic process, detoxification, regulation of peptidase activity, organic anion transport, inflammatory response, negative regulation of cell death, fatty acid metabolic process, lipid metabolic process, divalent inorganic cation homeostasis, regulation of endocytosis, alcohol metabolic process, immune response, cellular lipid metabolic process, monocarboxylic acid transport, negative regulation of apoptotic signaling pathway, multicellular organismal homeostasis, organic hydroxy compound biosynthetic process, regulation of cell death, lipid catabolic process, regulation of lipid metabolic process, regulation of steroid metabolic process, regulation of inflammatory response, response to toxic substance, cellular chemical homeostasis, regulation of transport, regulation of lipid catabolic process, regulation of immune effector process, lipid localization, regulation of proteolysis, regulation of secretion, regulation of response to wounding, regulation of multicellular organismal process, cellular homeostasis, single organism catabolic process, response to oxidative stress, behavior, acute phase response, regulation of response to external stimulus, regulation of apoptotic signaling pathway, regulation of cell proliferation, response to reactive oxygen species, endocytic vesicle, endoplasmic reticulum part, endoplasmic reticulum lumen, endoplasmic reticulum, lipid transporter activity, sulfur compound binding, steroid binding, glycosaminoglycan binding, alcohol binding, carboxylic ester hydrolase activity, lipid binding, receptor binding, coenzyme binding, adipogenesis, xenobiotic metabolism, fatty acid metabolism, coagulation, bile acid metabolism, peroxisome, or a combination thereof.

Statement 5. The method of Statement 1 or 4, or the agent for use according to Statement 2 or 4, or the use according to Statement 3 or 4, wherein the method further comprises administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in HDAC3 targets, photodynamic therapy stress, CEBP targets, tolerant macrophage, response to salirasib, adult tissue stem module, klfl targets, anatomical structure formation involved in morphogenesis, circulatory system process, cellular response to external stimulus, response to wounding, cellular response to extracellular stimulus, cell activation, cellular response to oxygen containing compound, vesicle mediated transport, enzyme linked receptor protein signaling pathway, response to bacterium, regulation of catabolic process, response to ketone, regulation of cell adhesion, response to hormone, blood vessel morphogenesis, response to estrogen, response to radiation, response to extracellular stimulus, cellular response to nitrogen compound, regulation of catalytic activity, vasculature development, response to abiotic stimulus, response to drug, response to growth factor, regulation of protein metabolic process, transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to peptide, hexose metabolic process, cellular response to stress, endocytosis, circulatory system development, response to starvation, hemostasis, response to molecule of bacterial origin, cell surface, peptidase regulator activity, molecular function regulator, peptidase inhibitor activity, phospholipid binding, TNF-a signaling via NFkB, or a combination thereof.

Statement 6. The method of any one of Statements 1 or 4-5, or the agent for use according to any one of Statements 2 or 4-5, or the use according to any one of Statements 3-5, wherein the agent modulates expression and/or activity of one or more genes or gene products in Wnt pathway.

Statement 7. The method of any one of Statements 1 or 4-6, or the agent for use according to any one of Statements 2 or 4-6, or the use according to any one of Statements 3-6, wherein the agent modulates expression and/or activity of one or more genes or gene products that are markers of hepatic stem cells.

Statement 8. The method of any one of Statements 1 or 4-7, or the agent for use according to any one of Statements 2 or 4-7, or the use according to any one of Statements 3-7, wherein the expression and/or activity of the one or more genes or gene products is altered in response to a zone-dependent injury and a zone-independent injury.

Statement 9. The method of any one of Statements 1 or 4-8, or the agent for use according to any one of Statements 2 or 4-8, or the use according to any one of Statements 3-8, wherein the one or more genes or gene products comprises Gclc, Txnrd1, Lars2, Cyp4a14, Apoc2, Apoc1, Cyp2c29, Mt1, Mt2, Saa1, Saa2, Fgl1, Mup17, Mup18, Mup1, Gm23935, mmu-mir-6236, Ly6e, Rnase4, Saa4, Fgl1, Hp, Hpx, Lcn2, Orm1, Apcs, Orm2, Saa1, Saa2, Saa3, Sds, Tacc2, Igfbp1, Cxc11, Thrsp, Serpina3n, Lpin1, Steap4, Mt1, Mt2, Aldh3a2, Cyp2c37, Cyp2c29, Cyp8b1, Ces1d, Apoc1, Hsd17b, Atp5h, Apoc2, Retsat, Mat1a, Angptl3, Chchd10, Hmgcs2, Cyp4a10, Cyp4a14, Gm26917, Lars2, Hyou1, Arrdc3, Mup12, Gm15564, Pdia3, Gm26924, Sephs2, Grip2, Krt8, Krt18, Plin2, Chka, Gclc, Srxn1, Hmox1, S100a8, S100a9, Mup15, Mup4, Ankrd55, Mup11, Mup5, Mup18, Mup9, Mup6, Mup17, Mup19, Alb, Pck1, Slc2a2, F2, Cyp2e1, Glu1, Arg1, Cdh1, Gls2, Ppargc1a, Sox9, Tbx3, Lgr5, Axin2, or a combination thereof.

Statement 9. The method of any one of Statements 1 or 4-8, or the agent for use according to any one of Statements 2 or 4-8, or the use according to any one of Statements 3-8, wherein the one or more genes or gene products are selected from the genes or gene products in any one of Tables 1-8 or in all of Tables 1-8.

Statement 10. The method of any one of Statements 1 or 4-9, or the agent for use according to any one of Statements 2 or 4-9, or the use according to any one of Statements 3-9, wherein the agent induces regeneration of the organ or tissue.

Statement 11. The method of any one of Statements 1 or 4-9, or the agent for use according to any one of Statements 2 or 4-9, or the use according to any one of Statements 3-9, wherein the agent induces functional compensation of the organ or tissue.

Statement 12. The method of any one of Statements 1 or 4-9, or the agent for use according to any one of Statements 2 or 4-9, or the use according to any one of Statements 3-9, wherein the agent induces regeneration and functional compensation of the organ or tissue.

Statement 13. The method of any one of Statements 1 or 4-12, or the agent for use according to any one of Statements 2 or 4-12, or the use according to any one of Statements 3-12, wherein the agent induces generation of cells that compensate function loss caused by the injury in the organ or tissue.

Statement 14. The method of any one of Statements 1 or 4-13, or the agent for use according to any one of Statements 2 or 4-13, or the use according to any one of Statements 3-13, wherein the agent induces cell proliferation in the organ or tissue.

Statement 15. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is liver.

Statement 16. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is spleen.

Statement 17. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is intestine.

Statement 18. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is colon.

Statement 19. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is bone marrow.

Statement 20. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is an immune tissue or organ.

Statement 21. The method of any one of Statements 1 or 4-14, or the agent for use according to any one of Statements 2 or 4-14, or the use according to any one of Statements 3-14, wherein the organ or tissue is a tissue or organ of the gastrointestinal tract.

Statement 22. The method of any one of Statements 1 or 4-21, or the agent for use according to any one of Statements 2 or 4-21, or the use according to any one of Statements 3-21, wherein the injury is an acute injury.

Statement 23. The method of any one of Statements 1 or 4-21, or the agent for use according to any one of Statements 2 or 4-21, or the use according to any one of Statements 3-21, wherein the injury is a chronic injury.

Statement 24. The method of any one of Statements 1 or 4-23, or the agent for use according to any one of Statements 2 or 4-23, or the use according to any one of Statements 3-23, wherein the injury is caused by a metabolic insult.

Statement 25. The method of any one of Statements 1 or 4-23, or the agent for use according to any one of Statements 2 or 4-23, or the use according to any one of Statements 3-23, wherein the injury is caused by a toxic insult.

Statement 26. The method of any one of Statements 1 or 4-24, or the agent for use according to any one of Statements 2 or 4-24, or the use according to any one of Statements 3-24, wherein the injury is caused by high fat diet.

Statement 27. The method of any one of Statements 1 or 4-24, or the agent for use according to any one of Statements 2 or 4-24, or the use according to any one of Statements 3-24, wherein the organ or tissue is liver and the injury is caused by high fat diet.

Statement 28. The method of any one of Statements 1 or 4-23, or the agent for use according to any one of Statements 2 or 4-23, or the use according to any one of Statements 3-23, wherein the injury is caused by a disease.

Statement 29. The method of any one of Statements 1 or 4-23, or the agent for use according to any one of Statements 2 or 4-23, or the use according to any one of Statements 3-23, wherein the injury is caused by a chronic disease.

Statement 30. The method of any one of Statements 1 or 4-23, or the agent for use according to any one of Statements 2 or 4-23, or the use according to any one of Statements 3-23, wherein the injury is caused by an acute disease.

Statement 31. The method of any one of Statements 1, 4-23 or 28-30, or the agent for use according to any one of Statements 2, 4-23 or 28-30, or the use according to any one of Statements 3-2.3 or 28-30, wherein the disease is a liver disease.

Statement 32. The method of Statement 31, or the agent for use according to Statement 31, or the use according to Statement 31, wherein the liver disease is non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or cirrhosis.

Statement 33. The method of any one of Statements 1 or 4-32, or the agent for use according to any one of Statements 2 or 4-32, or the use according to any one of Statements 3-32, wherein the injury is a zone-independent injury.

Statement 34. The method of any one of Statements 1 or 4-32, or the agent for use according to any one of Statements 2 or 4-32, or the use according to any one of Statements 3-32, wherein the injury is a zone-dependent injury.

Statement 35. The method of Statement 34, or the agent for use according to Statement 34, or the use according to Statement 34, wherein the injury is mainly to or substantially only to pericentral hepatocytes.

Statement 36. The method of Statement 34, or the agent for use according to Statement 34, or the use according to Statement 34, wherein the injury is mainly to or substantially only to periportal hepatocytes.

Statement 37. The method of any one of Statements 1 or 4-36, or the agent for use according to any one of Statements 2 or 4-36, or the use according to any one of Statements 3-36, wherein the subject is a human.

Statement 38. The method of any one of Statements 1 or 4-36, or the agent for use according to any one of Statements 2 or 4-36, or the use according to any one of Statements 3-36, wherein the subject is a non-human animal.

Statement 39. The method of any one of Statements 1 or 4-36, or the agent for use according to any one of Statements 2 or 4-36, or the use according to any one of Statements 3-36, wherein the subject is a non-human mammal.

Statement 40. A method of treating an injury in an organ or tissue, comprising:

-   -   determining expression of one or more genes from single cells in         the organ or tissue at a first time point and a second time         point;     -   selecting a first subset of genes from the one or more genes,         wherein expression of the first subset of genes at the first and         the second time points are different;     -   determining spatial locations of cells expressing the first         subset of genes in the organ or tissue at the first and the         second time points by an in situ hybridization assay; and     -   selecting a second subset of genes based on the spatial         locations of the cells expressing the second subset of genes     -   administering an agent that modulates expression and/or activity         of one or more of the second subset of genes to a subject in         need thereof.

Statement 41. A method of treating an injury in an organ or tissue comprising-administering an agent that modulates expression and/or activity of one or more of a second subset of genes to a subject in need thereof, wherein said second subset of genes has been selected by a method comprising:

-   -   determining expression of one or more genes from single cells in         the organ or tissue at a first time point and a second time         point;     -   selecting a first subset of genes from the one or more genes,         wherein expression of the first subset of genes at the first and         the second time points are different;     -   determining spatial locations of cells expressing the first         subset of genes in the organ or tissue at the first and the         second time points by an in situ hybridization assay; and     -   selecting the second subset of genes based on the spatial         locations of the cells expressing the second subset of genes.

Statement 42. An agent that modulates expression and/or activity of one or more of a second subset of genes for use in a method of treating an injury in an organ or tissue, wherein said second subset of genes has been selected by a method comprising:

-   -   determining expression of one or more genes from single cells in         the organ or tissue at a first time point and a second time         point;     -   selecting a first subset of genes from the one or more genes,         wherein expression of the first subset of genes at the first and         the second time points are different;     -   determining spatial locations of cells expressing the first         subset of genes in the organ or tissue at the first and the         second time points by an in situ hybridization assay; and     -   selecting the second subset of genes based on the spatial         locations of the cells expressing the second subset of genes.

EXAMPLES Example 1: High Resolution Characterization of the Liver's Response to Acute Injury

Dynamics of liver regeneration have been studied extensively utilizing toxic insult models, such as APAP, but also relying heavily on the partial hepatectomy model, in which liver mass is surgically resected. These methods can differ dramatically because of the nature of the insult driving the loss of functional tissue mass: APAP overdose results in extreme oxidative stress, mitochondrial dysfunction and zone-dependent damage, whereas zone-independent partial hepatectomy (PH) is simply removal of tissue in a zone-independent manner. (FIG. 1A).

Studies surrounding liver regeneration have primarily focused on the regeneration of lost cellular mass through a proliferative response. Massively-parallel single-cell RNA-sequencing (scRNA-seq) was deployed on thousands of hepatocytes, before, during and after the proliferative phase, in order to assess changes in the transcriptional profile of the liver following zone-dependent (APAP) compared to zone-independent (PH) injury. To add spatial context and validation of the scRNA-seq results, Applicants have coupled this analysis with single molecule fluorescence in situ hybridization (smFISH) in order to measure and quantify the mRNA content of hepatocytes within the mouse liver (FIG. 1A). Applicants have performed these analyses across a dynamic time course in order to assess the transcriptional environment during injury, recovery, and termination phases of liver regeneration (FIG. 1B). This has allowed us to characterize the hepatic regenerative response at a high-resolution revealing the ability of hepatocytes to adapt to decreased functional capacity following a loss of tissue mass due to injury.

To assess the transcriptional response of hepatocytes following acute injury, Applicants applied seq-well, a low-cost, high throughput platform for single-cell mRNA sequencing (scRNA-Seq) (Gierahn et al., Nature Methods 2017) to single cell suspensions obtained from livers from male mice (FIG. 1A, Methods). The seq-well technique relies on gently settling cells into wells by gravity, rather than pairing cells and beads through fluidics, thus reducing harsh processing and making seq-well ideal for fragile and sensitive cell types, such as hepatocytes. After sequencing and estimating gene expression levels, normalization was applied (Methods).

Application of dimensional reduction technique, t-Stochastic Neighbour Embedding (t-SNE), to the dataset revealed a diverse population of cells. While the processing methods enriched for hepatocytes over non-parenchymal cells, some non-parenchymal cells were still present, especially under conditions which experienced immune infiltration (Methods, filter to include hepatocytes only with all samples grouping together in lower PCs, with higher PCs separate by sample. tSNE run to visualize top 13 PCs). Data was subsetted to include only clusters of hepatocytes for further analysis, which revealed distinct separation by condition (FIG. 2 a ). Interestingly, the introduction of a stressor—acute injury by APAP or PH—forced hepatocytes to become more similar between biological replicates, forming unified clusters in tSNE space for each acute injury condition, as opposed to UT cells, which separated by individual. Without being bound by theory, it is believed that UT variation may be due to the innate heterogeneity of the liver during quiescence and may be influenced by numerous uncontrolled factors. This appears to represent a high level of baseline diversity in the control hepatocytes, but following stimulation, the liver damage response drives the expression patterns to become more similar between animals within a particular condition.

To assess pericentral and periportal gene expression patterns, module scores were calculated for pericentral hepatocyte (PCH) and periportal hepatocyte (PPH) gene lists over the full dataset. Table 1a provides gene expression markers for each treatment (APAP, PH and UT and each time point.

TABLE 1a Gene expression markers for each treatment (APAP, PH and UT) and each time point. p_val avg_logFC pct.1 pct.2 p_val_adj cluster gene S100a9 0 1.335714143 0.399 0.014 0 A6 S100a9 (APAP 6 hr) S100a8 0 1.116303013 0.353 0.012 0 A6 S100a8 Mmp8  5.57E−283 0.358500766 0.136 0  1.38E−278 A6 Mmp8 Srgn  2.57E−279 0.926041531 0.284 0.014  6.38E−275 A6 Srgn Hmox1  8.93E−278 1.29024983 0.558 0.074  2.22E−273 A6 Hmox1 Psat1  2.17E−268 0.300087383 0.229 0.008  5.39E−264 A6 Psat1 Il1b  8.17E−262 0.736545761 0.236 0.009  2.03E−257 A6 Il1b Srxn1  3.54E−259 1.874073335 0.821 0.24  8.79E−255 A6 Srxn1 Tnfrsf12a  2.15E−248 1.081418539 0.623 0.112  5.33E−244 A6 Tnfrsf12a Retnlg  2.07E−215 0.374568433 0.129 0.002  5.13E−211 A6 Retnlg Gclc  1.14E−211 1.892741272 0.962 0.737  2.83E−207 A6 Gclc Hilpda  1.84E−209 0.769838994 0.403 0.048  4.57E−205 A6 Hilpda Hba-a1  6.50E−198 0.715982212 0.165 0.005  1.61E−193 A6 Hba-a1 Clec4d  8.02E−190 0.262215609 0.107 0.001  1.99E−185 A6 Clec4d Ppl  3.63E−182 0.82872871 0.47 0.078  9.02E−178 A6 Ppl Nid1  2.61E−181 0.331498174 0.229 0.015  6.49E−177 A6 Nid1 Ccl6  1.21E−174 0.755214086 0.274 0.024  3.00E−170 A6 Ccl6 Il1r2  3.81E−173 0.322216828 0.117 0.002  9.47E−169 A6 Il1r2 Cd14  2.02E−167 0.358694149 0.153 0.006  5.01E−163 A6 Cd14 Chka  5.96E−161 1.386835525 0.716 0.245  1.48E−156 A6 Chka Plin2  2.06E−159 1.276258881 0.943 0.768  5.12E−155 A6 Plin2 Hba-a2  8.30E−156 0.532797826 0.131 0.004  2.06E−151 A6 Hba-a2 Slc16a6  5.60E−149 0.864031798 0.47 0.096  1.39E−144 A6 Slc16a6 Actb  3.73E−148 0.886001814 0.979 0.918  9.26E−144 A6 Actb Fxyd5  7.74E−138 0.269743073 0.138 0.006  1.92E−133 A6 Fxyd5 Txnrd1  1.12E−137 1.301320776 0.838 0.551  2.77E−133 A6 Txnrd1 Cdkn1a  4.35E−127 1.099461278 0.702 0.285  1.08E−122 A6 Cdkn1a Pla2g7  1.92E−121 0.273740007 0.119 0.005  4.77E−117 A6 Pla2g7 Mthfd2  2.58E−119 0.259977893 0.205 0.02  6.41E−115 A6 Mthfd2 Krt18  5.57E−119 1.117912275 0.864 0.686  1.38E−114 A6 Krt18 Plek  2.02E−118 0.303053621 0.11 0.004  5.02E−114 A6 Plek Krt8  2.55E−117 1.204053446 0.826 0.587  6.33E−113 A6 Krt8 Ptprc  7.05E−112 0.407223706 0.153 0.011  1.75E−107 A6 Ptprc Mt1  4.09E−110 0.931483521 0.981 0.75  1.02E−105 A6 Mt1 Tubb6  2.80E−105 0.533019897 0.368 0.075  6.95E−101 A6 Tubb6 Dusp5  6.83E−105 0.28888562 0.196 0.021  1.70E−100 A6 Dusp5 Cidec  6.14E−101 0.306758365 0.253 0.036 1.53E−96 A6 Cidec Gsta1 5.62E−86 0.42042238 0.32 0.067 1.40E−81 A6 Gsta1 Lrrc58 2.74E−81 0.924271525 0.711 0.444 6.81E−77 A6 Lrrc58 Rell1 8.51E−81 0.577000265 0.375 0.099 2.11E−76 A6 Rell1 C230081A13Rik 1.83E−80 0.414792324 0.279 0.055 4.54E−76 A6 C230081A13Rik Tyrobp 2.44E−79 0.443113689 0.189 0.026 6.06E−75 A6 Tyrobp Mt2 6.45E−79 0.664695984 0.938 0.619 1.60E−74 A6 Mt2 Rnf144a 4.17E−75 0.311931338 0.177 0.023 1.03E−70 A6 Rnf144a Plscr1 5.66E−75 0.434306904 0.329 0.081 1.40E−70 A6 Plscr1 Alb 1.63E−71 0.418074924 1 1 4.06E−67 A6 Alb Cd44 1.51E−70 0.292904911 0.115 0.01 3.75E−66 A6 Cd44 Il1r1 1.26E−69 0.844988554 0.683 0.392 3.13E−65 A6 Il1r1 Cers6 2.65E−69 0.477445769 0.332 0.086 6.58E−65 A6 Cers6 Cd53 8.74E−69 0.256050768 0.103 0.008 2.17E−64 A6 Cd53 Ets2 2.70E−68 0.627666547 0.415 0.136 6.71E−64 A6 Ets2 Myh9 1.15E−67 0.866093547 0.718 0.481 2.86E−63 A6 Myh9 mmu-mir-6240 1.30E−66 1.082608953 0.413 0.134 3.24E−62 A6 mmu-mir-6240 Mrap 2.88E−66 0.826081002 0.606 0.338 7.16E−62 A6 Mrap Clec4f 6.33E−64 0.990882766 0.339 0.095 1.57E−59 A6 Clec4f Tmsb4x 2.22E−62 0.70513404 0.332 0.093 5.50E−58 A6 Tmsb4x Itgb2 1.07E−61 0.262839863 0.105 0.01 2.66E−57 A6 Itgb2 Cd74 6.70E−61 0.441857606 0.155 0.022 1.66E−56 A6 Cd74 Apoa4 1.82E−60 0.945027313 0.721 0.49 4.53E−56 A6 Apoa4 Bcl2l1 3.01E−60 0.686254569 0.501 0.228 7.48E−56 A6 Bcl2l1 H2-Eb1 7.87E−60 0.321369004 0.105 0.01 1.95E−55 A6 H2-Eb1 Fcgr3 1.06E−58 0.294045394 0.107 0.011 2.64E−54 A6 Fcgr3 Serpina3m 1.07E−58 0.606679439 0.85 0.813 2.65E−54 A6 Serpina3m Insig2 1.68E−58 0.683422171 0.854 0.809 4.18E−54 A6 Insig2 Vcam1 2.58E−58 0.437641865 0.134 0.017 6.40E−54 A6 Vcam1 Malat1 2.86E−58 1.108271971 0.871 0.695 7.10E−54 A6 Malat1 Ctss 3.09E−58 0.703071213 0.212 0.043 7.66E−54 A6 Ctss Cd163 4.80E−58 0.40657557 0.146 0.021 1.19E−53 A6 Cd163 Cd97 6.94E−57 0.330330436 0.115 0.013 1.72E−52 A6 Cd97 Sqstm1 9.94E−56 0.681739125 0.859 0.836 2.47E−51 A6 Sqstm1 Klf6 1.97E−55 0.612280921 0.382 0.13 4.88E−51 A6 Klf6 Cyp4a14 2.22E−55 0.599586688 0.776 0.484 5.52E−51 A6 Cyp4a14 Iqgap1 1.16E−54 0.434488409 0.162 0.027 2.87E−50 A6 Iqgap1 Eif5 1.78E−54 0.580165484 0.816 0.756 4.42E−50 A6 Eif5 H2-Ab1 1.51E−52 0.449067035 0.158 0.026 3.74E−48 A6 H2-Ab1 Rgs2 1.81E−49 0.380196243 0.138 0.022 4.48E−45 A6 Rgs2 2010003K11Rik 8.78E−49 0.487245683 0.396 0.15 2.18E−44 A6 2010003K11Rik Sat1 2.97E−48 0.66217907 0.47 0.222 7.37E−44 A6 Sat1 Laptm5 2.87E−47 0.316929935 0.124 0.018 7.13E−43 A6 Laptm5 Efhd2 1.77E−46 0.55453654 0.468 0.221 4.40E−42 A6 Efhd2 Trp53inp1 9.60E−46 0.838899515 0.637 0.432 2.38E−41 A6 Trp53inp1 Tubb2a 2.49E−44 0.783817377 0.618 0.44 6.17E−40 A6 Tubb2a Nop58 1.23E−43 0.585927781 0.492 0.25 3.05E−39 A6 Nop58 D10Wsu102e 6.28E−43 0.513399976 0.37 0.148 1.56E−38 A6 D10Wsu102e Lyz2 2.44E−42 0.652343138 0.234 0.065 6.06E−38 A6 Lyz2 Retsat 9.48E−42 0.480062983 0.845 0.785 2.35E−37 A6 Retsat Eif1a 7.82E−41 0.658533359 0.599 0.41 1.94E−36 A6 Eif1a Slc39a14 7.86E−41 0.672079236 0.678 0.528 1.95E−36 A6 Slc39a14 C1qb 9.66E−41 0.594567033 0.234 0.066 2.40E−36 A6 C1qb Rcan1 1.14E−40 0.572746322 0.425 0.191 2.82E−36 A6 Rcan1 Hnf4a 1.63E−40 0.559027113 0.835 0.834 4.05E−36 A6 Hnf4a Hsd17b13 2.02E−40 0.528446636 0.864 0.751 5.02E−36 A6 Hsd17b13 Msn 2.18E−40 0.250996496 0.105 0.015 5.43E−36 A6 Msn Sdc4 2.72E−40 0.441532524 0.909 0.91 6.75E−36 A6 Sdc4 Gm20594 8.83E−40 0.582505706 0.442 0.195 2.19E−35 A6 Gm20594 Picalm 2.41E−39 0.642536234 0.647 0.473 5.98E−35 A6 Picalm Epas1 4.29E−39 0.626428547 0.604 0.426 1.07E−34 A6 Epas1 Hic2 1.51E−38 0.26725951 0.15 0.031 3.75E−34 A6 Hic2 Cxadr 6.30E−38 0.61841577 0.606 0.428 1.56E−33 A6 Cxadr Ddx21 7.17E−38 0.639844169 0.535 0.327 1.78E−33 A6 Ddx21 Agpat9 1.20E−37 0.296765266 0.277 0.094 2.98E−33 A6 Agpat9 Csf1r 7.16E−37 0.643246591 0.184 0.047 1.78E−32 A6 Csf1r Rock2 3.22E−36 0.552475288 0.425 0.208 8.00E−32 A6 Rock2 C1qc 3.82E−36 0.54773051 0.172 0.042 9.50E−32 A6 C1qc Tra2a 5.16E−36 0.69171846 0.337 0.138 1.28E−31 A6 Tra2a Fam134b 1.18E−35 0.620176283 0.678 0.544 2.93E−31 A6 Fam134b Cltc 3.48E−35 0.634637641 0.661 0.519 8.64E−31 A6 Cltc Gm23388 1.61E−34 0.421585518 0.222 0.067 4.00E−30 A6 Gm23388 Eaf1 8.98E−34 0.50657558 0.427 0.221 2.23E−29 A6 Eaf1 Gcnt2 1.97E−33 0.461368158 0.372 0.169 4.89E−29 A6 Gcnt2 Gm24187 2.37E−33 0.396868602 0.2 0.057 5.89E−29 A6 Gm24187 Mat1a 3.75E−33 0.331703101 0.986 0.978 9.32E−29 A6 Mat1a C1qa 4.44E−33 0.471019029 0.174 0.046 1.10E−28 A6 C1qa Tjp2 3.98E−32 0.403000168 0.332 0.143 9.89E−28 A6 Tjp2 Lyst 2.03E−31 0.376687839 0.31 0.124 5.03E−27 A6 Lyst Ugdh 2.04E−31 0.556346523 0.721 0.671 5.07E−27 A6 Ugdh Dgkd 3.12E−31 0.346236575 0.282 0.109 7.74E−27 A6 Dgkd Cfp 6.42E−31 0.325079609 0.143 0.034 1.59E−26 A6 Cfp Mdn1 8.91E−31 0.293117859 0.251 0.088 2.21E−26 A6 Mdn1 Btg1 1.21E−30 0.426522166 0.356 0.163 3.00E−26 A6 Btg1 Apob 7.36E−30 0.356365368 0.99 0.989 1.83E−25 A6 Apob Gnl3 1.05E−29 0.476957552 0.501 0.307 2.60E−25 A6 Gnl3 Ctsl 1.40E−29 0.43840609 0.878 0.896 3.49E−25 A6 Ctsl Dot1l 1.84E−29 0.369470561 0.282 0.112 4.56E−25 A6 Dot1l 1700017B05Rik 2.19E−29 0.289389909 0.255 0.094 5.43E−25 A6 1700017B05Rik B4galt5 2.51E−29 0.401953614 0.332 0.15 6.23E−25 A6 B4galt5 Asl 3.01E−29 0.434010731 0.826 0.812 7.46E−25 A6 Asl Hif1a 6.99E−29 0.471910312 0.427 0.234 1.73E−24 A6 Hif1a Ddx3x 3.19E−28 0.48933628 0.692 0.617 7.91E−24 A6 Ddx3x Stk40 5.19E−28 0.487468435 0.382 0.196 1.29E−23 A6 Stk40 Jmjd1c 8.87E−28 0.526154806 0.47 0.278 2.20E−23 A6 Jmjd1c Ddx5 8.92E−28 0.473243903 0.685 0.582 2.21E−23 A6 Ddx5 Wfdc17 1.92E−27 0.417330221 0.177 0.053 4.78E−23 A6 Wfdc17 Bach1 5.63E−27 0.672377572 0.461 0.291 1.40E−22 A6 Bach1 Ppan 2.32E−26 0.265470715 0.255 0.1 5.77E−22 A6 Ppan Vsig4 5.27E−26 0.454206621 0.117 0.028 1.31E−21 A6 Vsig4 Spred1 7.20E−26 0.335134356 0.308 0.139 1.79E−21 A6 Spred1 Chic2 8.63E−26 0.389971062 0.37 0.194 2.14E−21 A6 Chic2 Myo1e 9.65E−26 0.491635416 0.475 0.296 2.40E−21 A6 Myo1e Gm26924 1.31E−25 0.302897605 1 1 3.24E−21 A6 Gm26924 Igfbp1 2.08E−25 0.595262474 0.792 0.774 5.17E−21 A6 Igfbp1 Gm15564 3.38E−25 0.607856981 0.983 0.977 8.41E−21 A6 Gm15564 Lpin2 7.01E−25 0.522681584 0.745 0.694 1.74E−20 A6 Lpin2 Cd5l 7.67E−25 0.566281793 0.21 0.077 1.90E−20 A6 Cd5l Tsr1 8.86E−25 0.31396368 0.341 0.166 2.20E−20 A6 Tsr1 Creb3l2 4.54E−24 0.336328333 0.329 0.158 1.13E−19 A6 Creb3l2 Ier5 5.39E−24 0.279704513 0.134 0.037 1.34E−19 A6 Ier5 Eef2 5.73E−24 0.351846239 0.9 0.908 1.42E−19 A6 Eef2 Tcerg1 5.75E−24 0.335808462 0.305 0.145 1.43E−19 A6 Tcerg1 Apobec1 6.53E−24 0.282426929 0.239 0.094 1.62E−19 A6 Apobec1 Stat3 7.26E−24 0.484579314 0.604 0.472 1.80E−19 A6 Stat3 Rora 7.34E−24 0.551440037 0.549 0.429 1.82E−19 A6 Rora Lars2 1.06E−23 0.588681759 1 0.997 2.63E−19 A6 Lars2 Tars 1.14E−23 0.476757207 0.666 0.586 2.84E−19 A6 Tars Xbp1 1.76E−23 0.440708121 0.692 0.658 4.38E−19 A6 Xbp1 Sdad1 2.65E−23 0.284425559 0.289 0.129 6.58E−19 A6 Sdad1 St3gal1 6.64E−23 0.434367435 0.473 0.313 1.65E−18 A6 St3gal1 Son 1.36E−22 0.434214467 0.601 0.452 3.37E−18 A6 Son Heatr1 1.43E−22 0.343295645 0.291 0.134 3.55E−18 A6 Heatr1 Ncl 5.14E−22 0.429184065 0.69 0.629 1.28E−17 A6 Ncl Iigp1 6.99E−22 0.611771994 0.78 0.811 1.74E−17 A6 Iigp1 Rad54l2 7.85E−22 0.336619848 0.325 0.162 1.95E−17 A6 Rad54l2 Btg2 2.09E−21 0.538770616 0.549 0.401 5.20E−17 A6 Btg2 Tnfrsf1a 3.42E−21 0.453257878 0.508 0.37 8.49E−17 A6 Tnfrsf1a Mat2a 3.46E−21 0.469344192 0.487 0.336 8.58E−17 A6 Mat2a Itih2 4.13E−21 0.310907717 0.893 0.927 1.03E−16 A6 Itih2 Gtpbp4 4.40E−21 0.457875649 0.477 0.321 1.09E−16 A6 Gtpbp4 Dkc1 4.62E−21 0.323244532 0.315 0.159 1.15E−16 A6 Dkc1 Sdc3 4.87E−21 0.317989769 0.103 0.026 1.21E−16 A6 Sdc3 H3f3b 5.06E−21 0.508752641 0.613 0.515 1.26E−16 A6 H3f3b Neat1 6.54E−21 0.623425327 0.31 0.158 1.62E−16 A6 Neat1 Ces1d 1.34E−20 0.385383868 0.859 0.86 3.33E−16 A6 Ces1d Gm24245 1.85E−20 0.573742943 0.422 0.246 4.58E−16 A6 Gm24245 Maff 1.91E−20 0.331354317 0.224 0.095 4.75E−16 A6 Maff Mfsd2a 1.92E−20 0.423246315 0.465 0.309 4.78E−16 A6 Mfsd2a Hnrnpdl 2.52E−20 0.413693336 0.406 0.246 6.25E−16 A6 Hnrnpdl Phc2 2.87E−20 0.309159237 0.284 0.138 7.12E−16 A6 Phc2 Dusp16 2.97E−20 0.415286337 0.372 0.218 7.37E−16 A6 Dusp16 Tsku 3.12E−20 0.32057443 0.327 0.169 7.76E−16 A6 Tsku Lgmn 4.82E−20 0.436793121 0.246 0.11 1.20E−15 A6 Lgmn Etnppl 6.12E−20 0.403812162 0.706 0.572 1.52E−15 A6 Etnppl Abca1 1.01E−19 0.505812774 0.604 0.512 2.51E−15 A6 Abca1 Etf1 1.42E−19 0.447016025 0.606 0.507 3.53E−15 A6 Etf1 Pigr 2.32E−19 0.262735133 0.947 0.941 5.76E−15 A6 Pigr Ranbp2 3.87E−19 0.480806807 0.566 0.451 9.61E−15 A6 Ranbp2 Myl12a 5.48E−19 0.393725064 0.461 0.314 1.36E−14 A6 Myl12a Tiparp 7.18E−19 0.427006824 0.346 0.193 1.78E−14 A6 Tiparp Fam107b 7.48E−19 0.422395853 0.449 0.309 1.86E−14 A6 Fam107b Gm10800 8.12E−19 0.538348955 0.115 0.034 2.02E−14 A6 Gm10800 Nop56 1.10E−18 0.250694624 0.282 0.137 2.73E−14 A6 Nop56 Tsc22d2 1.20E−18 0.338155823 0.353 0.201 2.97E−14 A6 Tsc22d2 Tmem87b 1.51E−18 0.348646714 0.351 0.2 3.74E−14 A6 Tmem87b Jak1 1.86E−18 0.469606838 0.554 0.451 4.61E−14 A6 Jak1 Map2k3 3.65E−18 0.395195044 0.427 0.279 9.06E−14 A6 Map2k3 Stk17b 1.03E−17 0.282498896 0.126 0.041 2.56E−13 A6 Stk17b Nolc1 1.14E−17 0.408444859 0.363 0.215 2.82E−13 A6 Nolc1 Fcna 1.52E−17 0.346866554 0.124 0.04 3.77E−13 A6 Fcna Eif4g2 1.81E−17 0.339948168 0.757 0.774 4.50E−13 A6 Eif4g2 App 1.94E−17 0.329124793 0.315 0.17 4.83E−13 A6 App Gpt2 2.10E−17 0.368164282 0.764 0.787 5.22E−13 A6 Gpt2 Lmo4 3.07E−17 0.29230743 0.308 0.169 7.63E−13 A6 Lmo4 Mrc1 4.45E−17 0.306341468 0.131 0.044 1.10E−12 A6 Mrc1 Mmp14 4.96E−17 0.259424135 0.253 0.124 1.23E−12 A6 Mmp14 Abhd2 9.00E−17 0.359296116 0.37 0.221 2.24E−12 A6 Abhd2 Tatdn2 2.25E−16 0.309027814 0.334 0.189 5.59E−12 A6 Tatdn2 Tbc1d15 3.21E−16 0.419972242 0.461 0.337 7.98E−12 A6 Tbc1d15 Ywhag 4.64E−16 0.464937447 0.518 0.422 1.15E−11 A6 Ywhag Dusp6 1.09E−15 0.476849753 0.482 0.361 2.70E−11 A6 Dusp6 Mcl1 1.59E−15 0.463883705 0.573 0.468 3.94E−11 A6 Mcl1 Hspb8 1.99E−15 0.372641331 0.709 0.705 4.93E−11 A6 Hspb8 Epb4.1 2.12E−15 0.418931034 0.537 0.431 5.25E−11 A6 Epb4.1 Kif5b 3.44E−15 0.433974551 0.494 0.395 8.53E−11 A6 Kif5b Lrrfip1 5.10E−15 0.39715369 0.37 0.237 1.27E−10 A6 Lrrfip1 Cars 5.93E−15 0.278965519 0.329 0.192 1.47E−10 A6 Cars Zyx 6.80E−15 0.285048478 0.263 0.139 1.69E−10 A6 Zyx Gnl2 1.37E−14 0.333718771 0.384 0.253 3.41E−10 A6 Gnl2 Fndc3b 2.02E−14 0.297639516 0.315 0.184 5.01E−10 A6 Fndc3b Mybbp1a 2.24E−14 0.389680186 0.396 0.276 5.56E−10 A6 Mybbp1a Cyp4a10 2.95E−14 0.309701213 0.687 0.606 7.32E−10 A6 Cyp4a10 Ptpn1 2.99E−14 0.323913522 0.353 0.212 7.42E−10 A6 Ptpn1 Rn7sk 3.96E−14 0.324401888 0.339 0.203 9.83E−10 A6 Rn7sk Wdr43 4.52E−14 0.301347392 0.353 0.221 1.12E−09 A6 Wdr43 Cybb 5.80E−14 0.363939527 0.107 0.037 1.44E−09 A6 Cybb Wbp1l 5.81E−14 0.35324603 0.697 0.703 1.44E−09 A6 Wbp1l Plec 5.98E−14 0.355267946 0.422 0.289 1.48E−09 A6 Plec Slc20a1 9.62E−14 0.303408431 0.284 0.159 2.39E−09 A6 Slc20a1 Aff4 9.83E−14 0.483625144 0.537 0.448 2.44E−09 A6 Aff4 Tm4sf4 1.22E−13 0.383397009 0.484 0.379 3.04E−09 A6 Tm4sf4 Lcp1 1.53E−13 0.463298076 0.492 0.367 3.80E−09 A6 Lcp1 Ppp1r12a 1.74E−13 0.323279732 0.317 0.19 4.33E−09 A6 Ppp1r12a Prrc2c 1.85E−13 0.367548918 0.415 0.285 4.59E−09 A6 Prrc2c Cyp39a1 1.93E−13 0.292505843 0.305 0.183 4.80E−09 A6 Cyp39a1 Pxk 2.42E−13 0.256288767 0.303 0.177 6.01E−09 A6 Pxk St3gal5 5.27E−13 0.296275564 0.706 0.63 1.31E−08 A6 St3gal5 Lrrfip2 5.33E−13 0.352184936 0.384 0.258 1.32E−08 A6 Lrrfip2 Mbnl1 6.12E−13 0.362674779 0.492 0.386 1.52E−08 A6 Mbnl1 Fus 1.20E−12 0.334188564 0.394 0.277 2.98E−08 A6 Fus Pabpc1 1.23E−12 0.284772489 0.697 0.662 3.05E−08 A6 Pabpc1 Arhgef12 1.39E−12 0.426872316 0.578 0.523 3.46E−08 A6 Arhgef12 Stom 1.51E−12 0.27534126 0.329 0.208 3.75E−08 A6 Stom Srsf11 1.96E−12 0.380589282 0.418 0.299 4.86E−08 A6 Srsf11 Nars 2.53E−12 0.33663939 0.606 0.56 6.27E−08 A6 Nars Ptpn12 4.40E−12 0.297316891 0.263 0.15 1.09E−07 A6 Ptpn12 Palld 5.39E−12 0.29349618 0.353 0.232 1.34E−07 A6 Palld Il4ra 8.30E−12 0.257153801 0.248 0.137 2.06E−07 A6 Il4ra Ankrd11 1.52E−11 0.378964388 0.389 0.269 3.77E−07 A6 Ankrd11 Dst 1.78E−11 0.373962562 0.43 0.318 4.43E−07 A6 Dst Mki67ip 2.73E−11 0.298808984 0.344 0.227 6.77E−07 A6 Mki67ip Cald1 4.43E−11 0.283138123 0.766 0.799 1.10E−06 A6 Cald1 Phlda1 5.66E−11 0.451479481 0.494 0.445 1.41E−06 A6 Phlda1 Ifrd1 6.04E−11 0.44712839 0.365 0.25 1.50E−06 A6 Ifrd1 Pacsin2 6.38E−11 0.353993311 0.37 0.261 1.58E−06 A6 Pacsin2 Fkbp5 6.69E−11 0.307808382 0.415 0.29 1.66E−06 A6 Fkbp5 Smg1 7.01E−11 0.278924303 0.265 0.159 1.74E−06 A6 Smg1 Tns1 7.04E−11 0.32885739 0.403 0.299 1.75E−06 A6 Tns1 Gjb2 8.99E−11 0.324993861 0.678 0.703 2.23E−06 A6 Gjb2 Mak16 1.07E−10 0.271983271 0.267 0.159 2.65E−06 A6 Mak16 Map3k5 2.49E−10 0.27940085 0.346 0.234 6.19E−06 A6 Map3k5 Chd1 2.74E−10 0.281548083 0.377 0.27 6.80E−06 A6 Chd1 Kdelr2 3.61E−10 0.359811942 0.484 0.425 8.97E−06 A6 Kdelr2 Cast 3.73E−10 0.343500313 0.399 0.294 9.27E−06 A6 Cast Smap2 4.35E−10 0.319039862 0.363 0.25 1.08E−05 A6 Smap2 Purb 4.61E−10 0.29384642 0.341 0.236 1.14E−05 A6 Purb Man2a1 5.79E−10 0.274405257 0.671 0.689 1.44E−05 A6 Man2a1 Wdr26 5.81E−10 0.346830997 0.549 0.49 1.44E−05 A6 Wdr26 Sptbn1 7.00E−10 0.332175015 0.439 0.352 1.74E−05 A6 Sptbn1 Coro1c 1.40E−09 0.275517721 0.208 0.115 3.47E−05 A6 Coro1c Sfpq 1.53E−09 0.310914261 0.406 0.305 3.80E−05 A6 Sfpq Eif4g1 1.58E−09 0.274946516 0.723 0.737 3.92E−05 A6 Eif4g1 Gm5424 1.92E−09 0.319966931 0.411 0.312 4.78E−05 A6 Gm5424 AA474408 2.16E−09 0.267890734 0.274 0.172 5.37E−05 A6 AA474408 Ddx6 2.21E−09 0.368176844 0.527 0.459 5.49E−05 A6 Ddx6 Rbm25 2.60E−09 0.371600026 0.461 0.363 6.46E−05 A6 Rbm25 Akap13 2.60E−09 0.408483485 0.406 0.304 6.47E−05 A6 Akap13 Metap2 2.78E−09 0.304477182 0.453 0.371 6.89E−05 A6 Metap2 Chmp4b 3.12E−09 0.282546158 0.442 0.353 7.76E−05 A6 Chmp4b Atf4 3.46E−09 0.277274796 0.58 0.507 8.59E−05 A6 Atf4 Gsr 4.92E−09 0.367675526 0.453 0.367 0.0001221 A6 Gsr Slc4a4 5.68E−09 0.297606513 0.513 0.441 0.000140988 A6 Slc4a4 Uhrf1bp1l 6.07E−09 0.33260243 0.399 0.307 0.000150772 A6 Uhrf1bp1l Gsk3b 6.43E−09 0.329286038 0.384 0.29 0.000159674 A6 Gsk3b Atp2a2 6.85E−09 0.309886544 0.616 0.603 0.000170151 A6 Atp2a2 Reep3 7.41E−09 0.321347377 0.535 0.514 0.000183969 A6 Reep3 Tpr 9.24E−09 0.356753149 0.501 0.429 0.000229341 A6 Tpr Rnd3 9.97E−09 0.267699227 0.284 0.187 0.000247483 A6 Rnd3 Huwe1 1.28E−08 0.285654225 0.492 0.406 0.000318913 A6 Huwe1 Eif4a1 1.29E−08 0.275359204 0.418 0.327 0.000319298 A6 Eif4a1 Sf1 1.36E−08 0.257203905 0.351 0.248 0.000337793 A6 Sf1 Hmgcr 1.74E−08 0.346160341 0.425 0.342 0.000432829 A6 Hmgcr Grn 2.07E−08 0.295536999 0.582 0.55 0.000513486 A6 Grn Egr1 2.14E−08 0.370050393 0.589 0.54 0.0005325 A6 Egr1 Scaf11 2.17E−08 0.309964438 0.449 0.377 0.000539745 A6 Scaf11 Bptf 2.28E−08 0.275194478 0.332 0.232 0.000565519 A6 Bptf Tmed5 2.47E−08 0.272917209 0.594 0.583 0.000612693 A6 Tmed5 Sbno1 2.47E−08 0.299396593 0.394 0.306 0.000614253 A6 Sbno1 Dhx9 3.39E−08 0.285323361 0.427 0.339 0.000842741 A6 Dhx9 Slc40a1 4.45E−08 0.412382652 0.456 0.378 0.001105109 A6 Slc40a1 Lpgat1 4.50E−08 0.342974763 0.618 0.636 0.001117229 A6 Lpgat1 Gm26917 7.14E−08 0.299154579 0.382 0.289 0.001772559 A6 Gm26917 Birc6 8.11E−08 0.277616901 0.446 0.354 0.002013406 A6 Birc6 Rsl1d1 1.02E−07 0.303430543 0.47 0.411 0.002521012 A6 Rsl1d1 Hnrnpu 1.09E−07 0.28326413 0.625 0.639 0.002697817 A6 Hnrnpu Anxa5 1.15E−07 0.305834928 0.391 0.307 0.002851117 A6 Anxa5 Kif21a 1.26E−07 0.313315683 0.461 0.385 0.003128928 A6 Kif21a Gtf2a2 1.39E−07 0.251999937 0.379 0.292 0.003462804 A6 Gtf2a2 Akap11 1.43E−07 0.270661136 0.351 0.259 0.00355934 A6 Akap11 Clic4 1.72E−07 0.264181697 0.368 0.283 0.004262249 A6 Clic4 Mapkapk2 2.32E−07 0.294517429 0.396 0.311 0.005755355 A6 Mapkapk2 Atp13a3 2.93E−07 0.292349764 0.532 0.505 0.007280754 A6 Atp13a3 Net1 3.22E−07 0.306659682 0.408 0.332 0.007991182 A6 Net1 Zbtb20 3.23E−07 0.327627617 0.566 0.539 0.008021841 A6 Zbtb20 Rlim 9.49E−07 0.252627877 0.305 0.22 0.02357139 A6 Rlim Actr3 1.12E−06 0.25984234 0.36 0.28 0.027851102 A6 Actr3 Tnks2 1.30E−06 0.254002601 0.358 0.281 0.032193406 A6 Tnks2 BC005537 1.32E−06 0.289191965 0.544 0.509 0.03283521 A6 BC005537 Chuk 1.38E−06 0.310357965 0.523 0.489 0.034209316 A6 Chuk Phf20l1 1.39E−06 0.265257027 0.372 0.292 0.03450551 A6 Phf20l1 Mdm2 1.67E−06 0.259049205 0.305 0.222 0.041535876 A6 Mdm2 Brd2 2.12E−06 0.433254813 0.542 0.504 0.052591494 A6 Brd2 Atp2b1 2.38E−06 0.280653791 0.334 0.254 0.05897613 A6 Atp2b1 Mpeg1 4.38E−06 0.352914126 0.263 0.183 0.108746855 A6 Mpeg1 4932438A13Rik 7.01E−06 0.266199526 0.329 0.251 0.174064494 A6 4932438A13Rik Dnajc5 7.09E−06 0.250353453 0.372 0.308 0.176120819 A6 Dnajc5 Mgea5 7.20E−06 0.275686568 0.413 0.342 0.178891521 A6 Mgea5 Dync1h1 9.59E−06 0.282699593 0.379 0.306 0.238121164 A6 Dync1h1 Srsf5 1.19E−05 0.291409476 0.387 0.322 0.296477533 A6 Srsf5 Srrm2 1.36E−05 0.260727453 0.456 0.397 0.338662468 A6 Srrm2 Ddx3y 1.38E−05 0.288586131 0.47 0.429 0.342849995 A6 Ddx3y Kdm5a 1.60E−05 0.304429913 0.308 0.231 0.396217599 A6 Kdm5a Xrn2 1.82E−05 0.259675732 0.387 0.321 0.450954074 A6 Xrn2 Dnaja2 2.12E−05 0.279328244 0.516 0.493 0.52548196 A6 Dnaja2 Eif4ebp1 3.29E−05 0.259521234 0.387 0.328 0.817137366 A6 Eif4ebp1 Zfand5 3.57E−05 0.275089578 0.401 0.339 0.887556739 A6 Zfand5 Plk3 3.83E−05 0.283547851 0.413 0.346 0.951959871 A6 Plk3 Macf1 5.05E−05 0.301160502 0.377 0.313 1 A6 Macf1 Pi4k2a 6.34E−05 0.305951761 0.425 0.391 1 A6 Pi4k2a Lrrc59 6.81E−05 0.259229523 0.422 0.382 1 A6 Lrrc59 Eprs 7.81E−05 0.269947199 0.566 0.572 1 A6 Eprs Diap1 9.69E−05 0.270444484 0.382 0.318 1 A6 Diap1 Ctsb 0.000138715 0.323201059 0.804 0.852 1 A6 Ctsb Tab2 0.000169421 0.286847887 0.425 0.382 1 A6 Tab2 Rnf169 0.000193224 0.282809956 0.315 0.253 1 A6 Rnf169 Rap1b 0.000204185 0.259227104 0.406 0.355 1 A6 Rap1b Abcc2 0.000314242 0.250146223 0.632 0.663 1 A6 Abcc2 Eif4b 0.000334975 0.262813454 0.542 0.538 1 A6 Eif4b Kif1b 0.00036934 0.299926146 0.527 0.513 1 A6 Kif1b Zfp106 0.000422039 0.266717149 0.391 0.337 1 A6 Zfp106 Hectd1 0.00059151 0.251508749 0.547 0.536 1 A6 Hectd1 Nrp1 0.000622747 0.252678382 0.391 0.344 1 A6 Nrp1 Impad1 0.001316802 0.254658012 0.391 0.355 1 A6 Impad1 Atp1a1 0.001836487 0.262331948 0.53 0.561 1 A6 Atp1a1 Riok3 0.004729208 0.256616769 0.43 0.412 1 A6 Riok3 Trip11 0.005826406 0.273288464 0.341 0.302 1 A6 Trip11 Tln1 0.008537106 0.278523779 0.31 0.269 1 A6 Tln1 Grip2 0 0.877662322 0.475 0.002 0 A24 Grip2 Sephs21  8.05E−198 0.61331088 0.949 0.833  2.00E−193 A24 Sephs2 Gm269241  1.37E−184 0.628825902 1 1  3.39E−180 A24 Gm26924 Sepp1  4.76E−166 0.318542032 1 1  1.18E−161 A24 Sepp1 Hsp90b11  9.73E−149 0.509570205 0.954 0.95  2.42E−144 A24 Hsp90b1 Hspa5  1.96E−146 0.449684973 0.974 0.965  4.87E−142 A24 Hspa5 Pdia31  2.07E−144 0.546318119 0.895 0.824  5.14E−140 A24 Pdia3 Mup71  6.46E−140 0.375529532 0.985 0.969  1.60E−135 A24 Mup7 Gm155641  1.14E−129 1.14097252 0.982 0.976  2.83E−125 A24 Gm15564 Calr1  1.88E−129 0.45086474 0.952 0.906  4.67E−125 A24 Calr Fgb  5.44E−127 0.367238117 1 0.999  1.35E−122 A24 Fgb Mup121  6.26E−126 0.68150125 0.799 0.668  1.56E−121 A24 Mup12 Arrdc3  8.88E−116 0.54775482 0.52 0.24  2.21E−111 A24 Arrdc3 Hyou1  1.13E−113 0.638165516 0.717 0.515  2.82E−109 A24 Hyou1 Lars21  3.10E−111 1.041057155 0.998 0.997  7.70E−107 A24 Lars2 Sc5d1 6.21E−89 0.412371965 0.879 0.816 1.54E−84 A24 Sc5d C8b1 1.11E−85 0.384982182 0.898 0.879 2.75E−81 A24 C8b Fgg 1.64E−84 0.272181625 0.999 0.996 4.06E−80 A24 Fgg Fga 9.15E−71 0.254248466 0.998 0.997 2.27E−66 A24 Fga Hsd3b51 9.32E−70 0.441836795 0.638 0.418 2.31E−65 A24 Hsd3b5 Dnajc3 6.35E−69 0.392858395 0.85 0.813 1.58E−64 A24 Dnajc3 Pgrmc1 2.43E−68 0.289998299 0.953 0.949 6.04E−64 A24 Pgrmc1 Hdlbp 3.97E−68 0.408547423 0.853 0.783 9.86E−64 A24 Hdlbp Ssr3 2.31E−65 0.403074533 0.765 0.675 5.74E−61 A24 Ssr3 Pdia41 5.72E−65 0.459428501 0.733 0.644 1.42E−60 A24 Pdia4 Creld2 5.19E−64 0.485966761 0.583 0.403 1.29E−59 A24 Creld2 Glud1 5.85E−61 0.27854336 0.958 0.939 1.45E−56 A24 Glud1 Pdcd41 4.60E−59 0.456773789 0.677 0.548 1.14E−54 A24 Pdcd4 Eef1a1 3.88E−58 0.322152231 0.919 0.882 9.63E−54 A24 Eef1a1 C91 2.86E−57 0.289294558 0.952 0.934 7.11E−53 A24 C9 Elovl2 1.70E−53 0.36774725 0.826 0.762 4.21E−49 A24 Elovl2 Tram1 9.96E−51 0.35532977 0.7 0.585 2.47E−46 A24 Tram1 Pdia61 2.91E−50 0.368367226 0.779 0.718 7.23E−46 A24 Pdia6 Serp1 9.85E−50 0.365823084 0.809 0.752 2.45E−45 A24 Serp1 Calm1 1.21E−48 0.348585861 0.794 0.77 3.01E−44 A24 Calm1 Manf 4.99E−48 0.400885006 0.632 0.507 1.24E−43 A24 Manf Insig1 7.91E−48 0.40460413 0.626 0.496 1.96E−43 A24 Insig1 Hao11 8.37E−47 0.329177975 0.83 0.789 2.08E−42 A24 Hao1 Nudt71 2.49E−46 0.282119575 0.884 0.799 6.20E−42 A24 Nudt7 AI1823711 1.39E−45 0.35855032 0.747 0.686 3.45E−41 A24 AI182371 Iigp11 2.89E−44 0.297964443 0.832 0.808 7.17E−40 A24 Iigp1 Egfr 7.06E−43 0.295191072 0.882 0.861 1.75E−38 A24 Egfr Aox31 3.70E−41 0.31657291 0.916 0.894 9.20E−37 A24 Aox3 Rpn1 6.65E−39 0.399582378 0.605 0.497 1.65E−34 A24 Rpn1 Tmem30a 1.31E−38 0.309658036 0.766 0.719 3.25E−34 A24 Tmem30a n-R5-8s1 4.55E−38 0.526714633 0.522 0.323 1.13E−33 A24 n-R5-8s1 Atxn1 7.15E−37 0.303135424 0.311 0.17 1.77E−32 A24 Atxn1 Nr1d2 9.32E−37 0.347216847 0.442 0.295 2.31E−32 A24 Nr1d2 Hspa13 2.28E−36 0.308966854 0.404 0.257 5.65E−32 A24 Hspa13 Cyp2c701 1.85E−35 0.259617473 0.89 0.868 4.60E−31 A24 Cyp2c70 Gm24601 2.21E−34 0.54562503 0.404 0.241 5.49E−30 A24 Gm24601 Spcs3 8.19E−34 0.329508814 0.483 0.358 2.03E−29 A24 Spcs3 Gm54241 1.03E−33 0.31004204 0.445 0.302 2.57E−29 A24 Gm5424 Tmed7 5.31E−33 0.326955086 0.563 0.446 1.32E−28 A24 Tmed7 Adh41 3.43E−32 0.338184013 0.667 0.56 8.51E−28 A24 Adh4 Eif4g21 2.08E−31 0.258833943 0.8 0.771 5.18E−27 A24 Eif4g2 Prkd31 3.77E−31 0.336938928 0.631 0.543 9.36E−27 A24 Prkd3 Myh91 3.86E−29 0.329906697 0.595 0.479 9.59E−25 A24 Myh9 Akr1c141 5.50E−29 0.284278295 0.74 0.701 1.37E−24 A24 Akr1c14 Hsd17b21 9.92E−29 0.264739028 0.758 0.706 2.46E−24 A24 Hsd17b2 Ostc 1.19E−28 0.289134091 0.514 0.385 2.96E−24 A24 Ostc Sdf2l1 1.69E−28 0.260614388 0.412 0.278 4.19E−24 A24 Sdf2l1 Gm242451 2.43E−28 0.479708393 0.369 0.241 6.03E−24 A24 Gm24245 Rdx1 3.10E−28 0.295224413 0.729 0.69 7.70E−24 A24 Rdx Uso1 6.01E−28 0.310192088 0.597 0.519 1.49E−23 A24 Uso1 Pnpla71 2.02E−26 0.295524363 0.678 0.604 5.02E−22 A24 Pnpla7 Atp8b1 3.46E−26 0.294111116 0.391 0.266 8.59E−22 A24 Atp8b1 AA4744081 2.18E−25 0.390602267 0.278 0.165 5.41E−21 A24 AA474408 Stard4 1.38E−24 0.309852489 0.559 0.461 3.43E−20 A24 Stard4 Cltc1 6.57E−24 0.285288939 0.61 0.516 1.63E−19 A24 Cltc Usp4 1.52E−23 0.272747149 0.476 0.361 3.78E−19 A24 Usp4 Cmah1 3.19E−23 0.295776656 0.607 0.532 7.93E−19 A24 Cmah Fndc3b1 1.08E−22 0.250245162 0.291 0.178 2.67E−18 A24 Fndc3b Gm269171 5.09E−22 0.581927547 0.391 0.282 1.26E−17 A24 Gm26917 Sec61b1 5.10E−22 0.264836278 0.549 0.461 1.27E−17 A24 Sec61b Acly 7.83E−22 0.300495396 0.597 0.503 1.94E−17 A24 Acly Srebf1 2.75E−21 0.287445553 0.439 0.334 6.83E−17 A24 Srebf1 Dnajb11 6.25E−21 0.299844177 0.557 0.485 1.55E−16 A24 Dnajb11 Dnajc12 8.12E−21 0.256463813 0.275 0.173 2.02E−16 A24 Dnajc12 Usp9x 2.28E−19 0.28533222 0.502 0.411 5.66E−15 A24 Usp9x Rab1 1.00E−18 0.258167749 0.588 0.527 2.49E−14 A24 Rab1 Arcn1 2.36E−18 0.259397317 0.53 0.447 5.86E−14 A24 Arcn1 Etnk1 9.72E−18 0.276144874 0.49 0.41 2.41E−13 A24 Etnk1 Ctnnb1 1.62E−17 0.250000942 0.566 0.498 4.03E−13 A24 Ctnnb1 Nedd4 3.77E−17 0.255257894 0.647 0.615 9.36E−13 A24 Nedd4 Magt1 2.47E−16 0.252990053 0.52 0.464 6.14E−12 A24 Magt1 Nab1 2.71E−16 0.253358398 0.491 0.408 6.73E−12 A24 Nab1 Ptprf1 3.30E−16 0.251224059 0.588 0.532 8.21E−12 A24 Ptprf Nars1 6.06E−14 0.265707299 0.593 0.558 1.50E−09 A24 Nars Cyp1a21 2.13E−06 0.25313456 0.699 0.709 0.052836876 A24 Cyp1a2 Cyp4a142 0 1.487902827 0.991 0.45 0 A48 Cyp4a14 Cyp4a102 0 1.156719472 0.991 0.574 0 A48 Cyp4a10 Hmgcs21 0 0.819620651 1 0.972 0 A48 Hmgcs2 Chchd102 0 0.813974324 0.995 0.931 0 A48 Chchd10 Angptl3 0 0.770515169 0.995 0.945 0 A48 Angptl3 Mat1a2 0 0.658541776 1 0.976 0 A48 Mat1a Apoe2 0 0.610213342 1 1 0 A48 Apoe Ces1c1 0 0.586094458 0.999 0.986 0 A48 Ces1c Apoh1  1.40E−296 0.535860118 0.998 0.982  3.47E−292 A48 Apoh Ttc361  3.49E−294 0.614534948 0.996 0.937  8.67E−290 A48 Ttc36 Retsat2  8.18E−294 0.873440086 0.988 0.769  2.03E−289 A48 Retsat Ugt2b52  3.37E−269 0.610774194 0.996 0.939  8.37E−265 A48 Ugt2b5 Apoc2  4.66E−262 0.814207924 0.98 0.82  1.16E−257 A48 Apoc2 Rdh71  1.24E−251 0.557485283 0.996 0.958  3.07E−247 A48 Rdh7 Rbp4  6.09E−248 0.513931452 1 0.996  1.51E−243 A48 Rbp4 Abcd2  3.35E−245 0.290615784 0.473 0.091  8.32E−241 A48 Abcd2 Dbp  1.52E−225 0.292912608 0.52 0.117  3.78E−221 A48 Dbp Atp5h2  1.28E−220 0.731224311 0.933 0.613  3.17E−216 A48 Atp5h Decr12  3.47E−218 0.594105071 0.96 0.679  8.62E−214 A48 Decr1 Slco1a4  5.77E−218 0.546576628 0.77 0.284  1.43E−213 A48 Slco1a4 Herpud11  9.23E−217 0.596486042 0.985 0.815  2.29E−212 A48 Herpud1 Cyp3a251  1.10E−215 0.506946657 0.995 0.884  2.72E−211 A48 Cyp3a25 Nr1i32  1.91E−205 0.573928423 0.814 0.331  4.75E−201 A48 Nr1i3 Agt1  1.51E−199 0.533913518 0.981 0.837  3.75E−195 A48 Agt Ephx21  5.54E−196 0.486375274 0.993 0.905  1.38E−191 A48 Ephx2 Reep61  1.39E−194 0.590173225 0.967 0.81  3.44E−190 A48 Reep6 F2  3.96E−192 0.376680538 0.999 0.974  9.83E−188 A48 F2 Mfsd2a2  1.42E−188 0.582749125 0.731 0.276  3.53E−184 A48 Mfsd2a Ahcy1  1.94E−186 0.473933613 0.988 0.858  4.82E−182 A48 Ahcy Fth1  1.04E−184 0.434153916 0.996 0.978  2.58E−180 A48 Fth1 Apoa51  2.80E−184 0.436646528 0.998 0.957  6.96E−180 A48 Apoa5 Snord1181  5.48E−184 0.528640807 0.766 0.303  1.36E−179 A48 Snord118 Hmgcl  2.36E−183 0.619035847 0.956 0.712  5.87E−179 A48 Hmgcl Oaf1  2.57E−183 0.561886634 0.969 0.776  6.38E−179 A48 Oaf Hdac111  8.97E−179 0.3963119 0.713 0.267  2.23E−174 A48 Hdac11 Ttr1  1.32E−175 0.420507995 1 0.999  3.28E−171 A48 Ttr Rpl38  5.45E−174 0.345542874 0.596 0.193  1.35E−169 A48 Rpl38 Ttpa  2.01E−169 0.475726856 0.991 0.885  4.99E−165 A48 Ttpa Rgs161  2.49E−168 0.380333199 0.601 0.193  6.19E−164 A48 Rgs16 Ech11  2.07E−167 0.525118681 0.98 0.808  5.15E−163 A48 Ech1 Ces1b  2.28E−167 0.530778378 0.838 0.434  5.66E−163 A48 Ces1b Gm6484  5.35E−166 0.375910184 0.627 0.213  1.33E−161 A48 Gm6484 Khk2  8.30E−162 0.533840979 0.982 0.866  2.06E−157 A48 Khk Cyp2a12  1.12E−161 0.520687928 0.981 0.872  2.78E−157 A48 Cyp2a12 Lims2  2.85E−161 0.393099584 0.679 0.266  7.08E−157 A48 Lims2 Prodh2  5.22E−160 0.517905408 0.918 0.61  1.30E−155 A48 Prodh2 Bnip32  5.10E−158 0.526170876 0.876 0.517  1.27E−153 A48 Bnip3 Aldob  9.73E−158 0.375754846 1 0.996  2.42E−153 A48 Aldob Slc25a471  1.66E−156 0.524948065 0.992 0.913  4.13E−152 A48 Slc25a47 Apoc42  3.51E−154 0.50531584 0.998 0.974  8.72E−150 A48 Apoc4 Lcat1  5.07E−154 0.47331748 0.973 0.796  1.26E−149 A48 Lcat Amy11  3.72E−153 0.494980149 0.943 0.644  9.23E−149 A48 Amy1 Tef  2.06E−152 0.316225396 0.651 0.241  5.12E−148 A48 Tef Hrg1  3.76E−150 0.435967486 0.987 0.867  9.34E−146 A48 Hrg Pabpc11  3.95E−150 0.511620216 0.912 0.64  9.80E−146 A48 Pabpc1 Serpina1d1  1.77E−149 0.356258396 0.997 0.974  4.39E−145 A48 Serpina1d Cdo11  4.20E−148 0.430080331 0.997 0.957  1.04E−143 A48 Cdo1 Mlycd1  1.59E−147 0.463720831 0.893 0.506  3.94E−143 A48 Mlycd Slc27a51  1.82E−147 0.410011543 0.987 0.897  4.52E−143 A48 Slc27a5 Gstt3  2.24E−147 0.38336004 0.737 0.302  5.56E−143 A48 Gstt3 Echs11  3.16E−147 0.492572199 0.971 0.812  7.85E−143 A48 Echs1 Serping11  2.48E−145 0.443468356 0.987 0.893  6.16E−141 A48 Serping1 Ndrg21  2.32E−144 0.349757727 1 0.945  5.75E−140 A48 Ndrg2 Vtn2  3.16E−144 0.363779131 1 0.986  7.86E−140 A48 Vtn Pnpla2  7.80E−143 0.345688119 0.687 0.28  1.94E−138 A48 Pnpla2 Ube2r21  6.65E−142 0.467949325 0.884 0.55  1.65E−137 A48 Ube2r2 Apoc12  1.83E−141 0.363822891 1 0.994  4.54E−137 A48 Apoc1 Cox6a12  5.35E−141 0.447227091 0.987 0.848  1.33E−136 A48 Cox6a1 Ahsg1  4.13E−140 0.250603949 1 0.999  1.02E−135 A48 Ahsg Apoc32  4.73E−140 0.363390224 1 0.982  1.17E−135 A48 Apoc3 Abcb4  7.97E−139 0.470174782 0.956 0.697  1.98E−134 A48 Abcb4 Slc25a101  2.28E−137 0.453932455 0.877 0.535  5.65E−133 A48 Slc25a10 Scand1  3.35E−137 0.258140676 0.579 0.204  8.31E−133 A48 Scand1 Cyp3a112  1.28E−136 0.49808554 1 0.997  3.19E−132 A48 Cyp3a11 Slc10a11  2.15E−136 0.456196482 0.984 0.842  5.33E−132 A48 Slc10a1 Cebpb2  1.30E−135 0.423057947 0.815 0.421  3.22E−131 A48 Cebpb Esrra  3.53E−134 0.251776143 0.546 0.19  8.77E−130 A48 Esrra F101  6.00E−134 0.387936432 0.989 0.899  1.49E−129 A48 F10 Creg1  1.75E−133 0.418044745 0.993 0.907  4.35E−129 A48 Creg1 Atp5b  4.40E−133 0.345066858 0.997 0.942  1.09E−128 A48 Atp5b Fcgrt1  1.52E−131 0.431405292 0.91 0.585  3.78E−127 A48 Fcgrt Syvn1  1.64E−130 0.286655562 0.603 0.228  4.06E−126 A48 Syvn1 Slc25a20  1.74E−130 0.42083621 0.877 0.51  4.31E−126 A48 Slc25a20 Rpl4  2.29E−130 0.374416508 0.987 0.914  5.69E−126 A48 Rpl4 G0s21  7.23E−130 0.42316466 0.692 0.297  1.80E−125 A48 G0s2 Gabarap1  4.55E−128 0.437625588 0.956 0.753  1.13E−123 A48 Gabarap Gltscr2  9.76E−128 0.375879873 0.83 0.445  2.42E−123 A48 Gltscr2 Aldh9a1  2.74E−127 0.414716257 0.964 0.776  6.79E−123 A48 Aldh9a1 Ctsh  1.74E−126 0.464904773 0.945 0.718  4.32E−122 A48 Ctsh Cox8a2  2.32E−126 0.520209572 0.89 0.63  5.76E−122 A48 Cox8a Tmbim61  6.05E−126 0.3566995 0.996 0.952  1.50E−121 A48 Tmbim6 Gys21  6.92E−126 0.418222807 0.784 0.403  1.72E−121 A48 Gys2 Etfb1  1.50E−125 0.354169101 0.996 0.93  3.73E−121 A48 Etfb Hsd17b131  3.50E−125 0.642674937 0.934 0.739  8.68E−121 A48 Hsd17b13 Decr2  3.28E−124 0.430802372 0.92 0.652  8.15E−120 A48 Decr2 Etnppl2  6.28E−124 0.604543103 0.866 0.551  1.56E−119 A48 Etnppl Tmbim4  1.38E−123 0.393095222 0.784 0.413  3.42E−119 A48 Tmbim4 Vnn3  3.25E−123 0.305389222 0.684 0.291  8.07E−119 A48 Vnn3 Slc40a11  2.35E−122 0.331978458 0.744 0.347  5.83E−118 A48 Slc40a1 Fam195a  1.14E−121 0.354389232 0.726 0.333  2.83E−117 A48 Fam195a Sdhc  2.25E−121 0.433373604 0.91 0.645  5.58E−117 A48 Sdhc Bfar  2.55E−121 0.301816412 0.742 0.331  6.32E−117 A48 Bfar Serpinf1  3.44E−121 0.395394253 0.976 0.857  8.54E−117 A48 Serpinf1 Atp5g31  6.91E−120 0.3996086 0.985 0.882  1.72E−115 A48 Atp5g3 Smlr1  2.43E−119 0.306487823 0.68 0.297  6.02E−115 A48 Smlr1 0610005C13Rik1  4.83E−119 0.397711899 0.944 0.655  1.20E−114 A48 0610005C13Rik Sec14l21  1.17E−118 0.388989397 0.98 0.844  2.90E−114 A48 Sec14l2 Cox5a1  1.82E−118 0.430264839 0.938 0.701  4.51E−114 A48 Cox5a Azgp1  2.02E−117 0.28364834 0.997 0.968  5.02E−113 A48 Azgp1 Slc37a41  3.91E−117 0.421081968 0.858 0.511  9.70E−113 A48 Slc37a4 Pbld11  6.09E−117 0.398937692 0.881 0.559  1.51E−112 A48 Pbld1 Abhd14b1  6.78E−116 0.41043543 0.885 0.565  1.68E−111 A48 Abhd14b Sh3glb1  1.76E−115 0.32589137 0.695 0.317  4.36E−111 A48 Sh3glb1 Acat1  9.40E−114 0.377331408 0.978 0.831  2.33E−109 A48 Acat1 Armc1  1.07E−113 0.2587072 0.632 0.263  2.66E−109 A48 Armc1 F12  3.14E−112 0.384983296 0.966 0.813  7.79E−108 A48 F12 Sdhd1  6.90E−112 0.48488077 0.891 0.652  1.71E−107 A48 Sdhd Atp5j1  7.69E−112 0.457478416 0.916 0.7  1.91E−107 A48 Atp5j Acadl1  1.25E−111 0.387890841 0.896 0.603  3.10E−107 A48 Acadl1 Tcea31  5.25E−111 0.393446905 0.825 0.466  1.30E−106 A48 Tcea3 Shmt11  1.48E−109 0.38266243 0.882 0.562  3.67E−105 A48 Shmt1 Cyp3a59  4.56E−109 0.26420294 0.723 0.324  1.13E−104 A48 Cyp3a59 Sult1a11  1.06E−108 0.38558712 0.963 0.758  2.64E−104 A48 Sult1a1 Plin51  1.53E−108 0.326445383 0.788 0.392  3.79E−104 A48 Plin5 Atp5k1  3.01E−107 0.40741303 0.935 0.666  7.47E−103 A48 Atp5k Sord1  9.47E−107 0.376343552 0.987 0.915  2.35E−102 A48 Sord Park7  1.57E−106 0.402994356 0.953 0.765  3.90E−102 A48 Park7 Gstt2  2.12E−104 0.323388931 0.754 0.375  5.26E−100 A48 Gstt2 Pbld2  1.70E−103 0.361852773 0.891 0.571 4.23E−99 A48 Pbld2 Abcc3  2.28E−103 0.407473287 0.859 0.548 5.65E−99 A48 Abcc3 Yipf3  2.68E−103 0.270153738 0.68 0.314 6.66E−99 A48 Yipf3 Brap  6.59E−102 0.339491607 0.829 0.478 1.64E−97 A48 Brap Ppara1  6.71E−101 0.344157474 0.831 0.469 1.67E−96 A48 Ppara Cyp2d26  1.85E−100 0.329292761 0.982 0.902 4.58E−96 A48 Cyp2d26 Sult1d11  4.70E−100 0.52821451 0.936 0.668 1.17E−95 A48 Sult1d1 Aspdh  8.32E−100 0.325986003 0.776 0.415 2.07E−95 A48 Aspdh St3gal52 4.74E−99 0.376555805 0.914 0.607 1.18E−94 A48 St3gal5 Ddb1 5.85E−99 0.337307537 0.83 0.482 1.45E−94 A48 Ddb1 Ifnar2 7.04E−99 0.283328433 0.731 0.356 1.75E−94 A48 Ifnar2 Mrpl43 1.55E−98 0.269199069 0.714 0.34 3.86E−94 A48 Mrpl43 Ugt2b361 2.72E−98 0.35027496 0.99 0.91 6.76E−94 A48 Ugt2b36 Acbd51 9.30E−98 0.351727998 0.943 0.704 2.31E−93 A48 Acbd5 Lamp11 1.45E−97 0.337729586 0.982 0.888 3.59E−93 A48 Lamp1 Ndufb22 2.71E−97 0.40700274 0.888 0.583 6.72E−93 A48 Ndufb2 Acot12 4.00E−97 0.309136906 0.825 0.459 9.93E−93 A48 Acot12 Dhrs41 5.62E−97 0.34200938 0.94 0.662 1.40E−92 A48 Dhrs4 Tmem219 6.15E−97 0.264654785 0.664 0.306 1.53E−92 A48 Tmem219 Akr1c19 1.41E−95 0.370522208 0.821 0.48 3.49E−91 A48 Akr1c19 Pigr1 1.63E−95 0.422360865 0.977 0.937 4.05E−91 A48 Pigr Hsd17b101 2.18E−95 0.445183738 0.927 0.681 5.42E−91 A48 Hsd17b10 Gsta2 2.29E−95 0.273359973 0.638 0.288 5.70E−91 A48 Gsta2 1600002H07Rik 3.87E−95 0.293949608 0.736 0.38 9.60E−91 A48 1600002H07Rik Upb11 5.45E−95 0.363137835 0.945 0.74 1.35E−90 A48 Upb1 Sco2 6.00E−95 0.316967022 0.808 0.448 1.49E−90 A48 Sco2 Slc27a2 5.90E−94 0.314567347 0.996 0.944 1.46E−89 A48 Slc27a2 Ces2a 6.30E−94 0.340367802 0.969 0.802 1.56E−89 A48 Ces2a Acsl11 9.87E−94 0.366805004 0.978 0.878 2.45E−89 A48 Acsl1 Ces1f 2.92E−93 0.353237242 0.97 0.785 7.26E−89 A48 Ces1f Usmg51 2.06E−92 0.417280438 0.755 0.427 5.11E−88 A48 Usmg5 Asgr21 2.67E−91 0.343090019 0.879 0.573 6.64E−87 A48 Asgr2 Cd1d1 3.09E−91 0.351797646 0.887 0.601 7.69E−87 A48 Cd1d1 Dcxr2 1.59E−90 0.351763208 0.884 0.585 3.95E−86 A48 Dcxr Cpt2 1.60E−90 0.321419422 0.807 0.466 3.96E−86 A48 Cpt2 Rabac1 3.41E−90 0.334311521 0.807 0.468 8.47E−86 A48 Rabac1 Zfp91 1.53E−89 0.322140173 0.855 0.531 3.79E−85 A48 Zfp91 Aldoa 2.71E−89 0.263527898 0.719 0.357 6.73E−85 A48 Aldoa Cyp2c54 5.42E−88 0.442677432 0.896 0.613 1.35E−83 A48 Cyp2c54 Gcdh1 7.24E−87 0.305992607 0.977 0.856 1.80E−82 A48 Gcdh Glrx5 9.19E−87 0.330848831 0.886 0.573 2.28E−82 A48 Glrx5 Snx3 3.01E−86 0.256221746 0.693 0.351 7.47E−82 A48 Snx3 Atf5 2.84E−85 0.354363257 0.909 0.654 7.06E−81 A48 Atf5 Creb3l3 3.83E−85 0.322778047 0.971 0.829 9.51E−81 A48 Creb3l3 Lipa1 4.93E−85 0.327721132 0.904 0.64 1.23E−80 A48 Lipa Stbd11 8.89E−85 0.266732483 0.725 0.373 2.21E−80 A48 Stbd1 Ninj1 1.13E−84 0.354210049 0.874 0.601 2.81E−80 A48 Ninj1 Ndufb101 3.61E−84 0.347097666 0.907 0.668 8.97E−80 A48 Ndufb10 Eef1d 3.98E−84 0.274526073 0.795 0.442 9.88E−80 A48 Eef1d Cp 7.52E−84 0.271474528 0.995 0.963 1.87E−79 A48 Cp Ces1d2 8.69E−84 0.332413333 0.984 0.849 2.16E−79 A48 Ces1d Pitpnb 9.69E−84 0.272561149 0.795 0.447 2.41E−79 A48 Pitpnb Camk2n11 1.18E−83 0.257842409 0.691 0.35 2.92E−79 A48 Camk2n1 Mia3 1.40E−83 0.337358626 0.91 0.636 3.47E−79 A48 Mia3 Aco2 3.85E−83 0.305389265 0.846 0.539 9.55E−79 A48 Aco2 Galk1 6.87E−83 0.268631662 0.718 0.368 1.71E−78 A48 Galk1 Gsto1 1.16E−82 0.339244623 0.818 0.508 2.87E−78 A48 Gsto1 Gchfr2 1.22E−82 0.36759752 0.953 0.735 3.02E−78 A48 Gchfr Cyp2c441 2.39E−82 0.392018859 0.924 0.718 5.94E−78 A48 Cyp2c44 Ndufs7 4.90E−82 0.288168011 0.847 0.511 1.22E−77 A48 Ndufs7 Fah1 6.81E−82 0.30390683 0.974 0.849 1.69E−77 A48 Fah Ggnbp2 8.77E−82 0.282129685 0.818 0.466 2.18E−77 A48 Ggnbp2 11-Mar 1.38E−81 0.29858018 0.984 0.881 3.42E−77 A48 1-Mar Anapc131 2.12E−81 0.276177491 0.768 0.429 5.28E−77 A48 Anapc13 Ctsd 2.25E−81 0.323706348 0.916 0.669 5.58E−77 A48 Ctsd Mgll 4.44E−81 0.319246054 0.844 0.518 1.10E−76 A48 Mgll Hspa82 5.70E−81 0.327389675 0.952 0.776 1.41E−76 A48 Hspa8 Gyk 1.19E−80 0.265772985 0.778 0.424 2.95E−76 A48 Gyk Grn1 1.60E−80 0.328395818 0.844 0.525 3.98E−76 A48 Grn Pla2g12b 2.48E−80 0.292440083 0.798 0.464 6.15E−76 A48 Pla2g12b Slc2a21 2.96E−80 0.341623888 0.824 0.509 7.36E−76 A48 Slc2a2 Sirt31 3.56E−80 0.258019667 0.724 0.387 8.85E−76 A48 Sirt3 Gm49521 7.39E−80 0.298551252 0.824 0.491 1.84E−75 A48 Gm4952 Rps27l2 1.61E−79 0.418112699 0.924 0.775 4.00E−75 A48 Rps27l Suds3 5.33E−79 0.255930607 0.74 0.4 1.32E−74 A48 Suds3 Klf9 5.80E−79 0.314463584 0.862 0.581 1.44E−74 A48 Klf9 Wbp1l1 1.37E−78 0.334193985 0.91 0.684 3.39E−74 A48 Wbp1l Ndufa131 3.89E−78 0.323295375 0.959 0.772 9.66E−74 A48 Ndufa13 Cyp8b12 4.42E−78 0.355675896 0.911 0.629 1.10E−73 A48 Cyp8b1 Mpc21 4.75E−78 0.384116346 0.953 0.817 1.18E−73 A48 Mpc2 Tmem371 3.68E−77 0.266162015 0.786 0.441 9.14E−73 A48 Tmem37 Ctage5 4.42E−77 0.331475 0.941 0.692 1.10E−72 A48 Ctage5 Dctn2 8.59E−77 0.255512392 0.803 0.452 2.13E−72 A48 Dctn2 Sfxn1 1.34E−76 0.339934169 0.822 0.528 3.32E−72 A48 Sfxn1 Hagh1 1.43E−76 0.365459582 0.959 0.835 3.55E−72 A48 Hagh Eci2 1.53E−76 0.309061425 0.944 0.714 3.80E−72 A48 Eci2 Ubxn4 3.43E−76 0.296243889 0.893 0.599 8.52E−72 A48 Ubxn4 Pccb 5.27E−76 0.308534663 0.901 0.645 1.31E−71 A48 Pccb Ndufs81 1.65E−75 0.338746392 0.854 0.589 4.09E−71 A48 Ndufs8 D17Wsu92e 2.26E−75 0.29017967 0.909 0.639 5.62E−71 A48 D17Wsu92e Oplah 7.71E−75 0.285269759 0.805 0.482 1.91E−70 A48 Oplah Eif51 1.05E−74 0.294961471 0.953 0.74 2.61E−70 A48 Eif5 Hsd11b1 2.39E−74 0.304583237 0.977 0.848 5.94E−70 A48 Hsd11b1 Gas51 8.55E−74 0.273894232 0.803 0.485 2.12E−69 A48 Gas5 Tgoln1 1.25E−73 0.317768081 0.891 0.617 3.10E−69 A48 Tgoln1 Gm2a 1.74E−73 0.286180358 0.827 0.504 4.33E−69 A48 Gm2a 1100001G20Rik1 6.60E−73 0.334854645 0.993 0.979 1.64E−68 A48 1100001G20Rik Arhgap5 7.80E−73 0.264113051 0.852 0.509 1.94E−68 A48 Arhgap5 Mtdh 1.96E−72 0.252366839 0.819 0.475 4.88E−68 A48 Mtdh Gpt 2.68E−72 0.29324715 0.94 0.748 6.66E−68 A48 Gpt Tspo1 3.58E−71 0.30737702 0.784 0.475 8.90E−67 A48 Tspo Hsbp11 7.86E−71 0.284796107 0.792 0.502 1.95E−66 A48 Hsbp1 Akr1d11 1.08E−70 0.28615505 0.852 0.546 2.68E−66 A48 Akr1d1 Ugp21 5.70E−70 0.315665196 0.945 0.744 1.42E−65 A48 Ugp2 Acadvl 5.43E−69 0.274895665 0.959 0.791 1.35E−64 A48 Acadvl Ndufv31 6.91E−68 0.263947933 0.868 0.574 1.72E−63 A48 Ndufv3 Uqcrfs1 1.53E−67 0.307020216 0.949 0.781 3.79E−63 A48 Uqcrfs1 Acadl 2.72E−67 0.270468066 0.916 0.655 6.76E−63 A48 Acadl Actn4 5.82E−66 0.253112911 0.789 0.489 1.44E−61 A48 Actn4 Ubxn1 7.62E−66 0.253917187 0.86 0.572 1.89E−61 A48 Ubxn1 Map2k2 8.71E−66 0.251107456 0.832 0.543 2.16E−61 A48 Map2k2 Dgat21 1.45E−65 0.283867124 0.947 0.761 3.60E−61 A48 Dgat2 Maob 1.61E−65 0.289210898 0.889 0.609 4.01E−61 A48 Maob Esd 1.67E−65 0.309040682 0.935 0.734 4.15E−61 A48 Esd Ccs1 1.06E−64 0.302390102 0.895 0.658 2.64E−60 A48 Ccs Slc25a13 1.33E−64 0.274023596 0.924 0.678 3.29E−60 A48 Slc25a13 Cyp2d101 2.32E−64 0.259489083 0.986 0.888 5.77E−60 A48 Cyp2d10 Eci1 8.76E−64 0.280304871 0.914 0.67 2.18E−59 A48 Eci1 Gpld1 1.63E−63 0.273116761 0.877 0.617 4.04E−59 A48 Gpld1 Hal1 2.04E−63 0.383784717 0.908 0.734 5.06E−59 A48 Hal Pglyrp2 2.50E−63 0.252927854 0.754 0.447 6.20E−59 A48 Pglyrp2 Car8 6.69E−63 0.276457751 0.765 0.459 1.66E−58 A48 Car8 Akr1c142 9.77E−63 0.29552724 0.92 0.685 2.43E−58 A48 Akr1c14 Abca6 2.25E−62 0.271013657 0.849 0.569 5.59E−58 A48 Abca6 Mst1 3.25E−62 0.256965699 0.81 0.517 8.06E−58 A48 Mst1 Lpin21 3.66E−62 0.30814041 0.921 0.675 9.09E−58 A48 Lpin2 Uroc1 5.97E−62 0.303202921 0.914 0.681 1.48E−57 A48 Uroc1 Dpys 7.13E−62 0.26481371 0.922 0.679 1.77E−57 A48 Dpys Furin 8.92E−62 0.256394896 0.781 0.481 2.21E−57 A48 Furin Slc25a39 1.17E−61 0.282702178 0.938 0.783 2.91E−57 A48 Slc25a39 Acaa1a1 1.53E−61 0.271027117 0.901 0.66 3.81E−57 A48 Acaa1a Fkbp2 2.98E−61 0.253151747 0.841 0.539 7.40E−57 A48 Fkbp2 Leap21 4.65E−61 0.374408905 0.833 0.566 1.15E−56 A48 Leap2 Pim31 4.96E−60 0.270043644 0.845 0.554 1.23E−55 A48 Pim3 Tmem14c1 6.44E−60 0.284049383 0.837 0.557 1.60E−55 A48 Tmem14c Uqcr101 3.87E−59 0.275943715 0.943 0.764 9.61E−55 A48 Uqcr10 Pemt1 3.70E−57 0.293943649 0.948 0.783 9.18E−53 A48 Pemt Hadh1 5.81E−57 0.254909361 0.908 0.668 1.44E−52 A48 Hadh Ndufb91 6.54E−57 0.284982242 0.982 0.855 1.62E−52 A48 Ndufb9 Os9 7.96E−57 0.250595723 0.911 0.694 1.98E−52 A48 Os9 Cyp2d22 9.72E−57 0.252444699 0.835 0.558 2.41E−52 A48 Cyp2d22 Mug1 2.07E−56 0.266350935 0.998 0.977 5.13E−52 A48 Mug1 Apoa42 2.43E−56 0.289005619 0.778 0.473 6.04E−52 A48 Apoa4 Ces1e 5.16E−56 0.252814514 0.864 0.565 1.28E−51 A48 Ces1e Baat1 1.58E−55 0.250789569 0.954 0.738 3.93E−51 A48 Baat Cideb2 2.02E−55 0.282394867 0.892 0.68 5.02E−51 A48 Cideb Atp5d1 2.52E−55 0.255861997 0.935 0.724 6.25E−51 A48 Atp5d Asl1 1.11E−54 0.348714359 0.953 0.8 2.75E−50 A48 Asl Ephx1 1.24E−54 0.261130074 0.933 0.767 3.08E−50 A48 Ephx1 Hadha 1.83E−54 0.266045541 0.943 0.762 4.55E−50 A48 Hadha Ehhadh 1.74E−52 0.268061208 0.908 0.66 4.32E−48 A48 Ehhadh Hint12 8.91E−51 0.299642398 0.954 0.812 2.21E−46 A48 Hint1 Cyb52 1.29E−50 0.332815798 0.992 0.977 3.20E−46 A48 Cyb5 Pcbd11 3.34E−47 0.255954233 0.932 0.818 8.30E−43 A48 Pcbd1 Hsd17b6 6.76E−44 0.325224319 0.646 0.387 1.68E−39 A48 Hsd17b6 Sds1 2.08E−43 0.355755983 0.799 0.625 5.18E−39 A48 Sds Cyp2f2 1.20E−31 0.288977869 0.912 0.81 2.99E−27 A48 Cyp2f2 Slco1b21 6.84E−29 0.302461427 0.996 0.931 1.70E−24 A48 Slco1b2 Cyp2a52 5.71E−06 0.370640229 0.518 0.393 0.141821036 A48 Cyp2a5 Cyp2c292 0.006241385 0.279136981 0.91 0.82 1 A48 Cyp2c29 Cyp4a143 0 1.209065936 0.975 0.456 0 A96 Cyp4a14 Apoc13 0 0.60439126 1 0.994 0 A96 Apoc1 Zfp683 0 0.535767012 0.476 0.054 0 A96 Zfp683 Cyp4a103  5.50E−304 1.099606992 0.974 0.58  1.36E−299 A96 Cyp4a10 Angptl31  7.63E−290 0.72518632 0.998 0.945  1.89E−285 A96 Angptl3 Apoa22  5.38E−255 0.433196336 1 0.999  1.34E−250 A96 Apoa2 Apoe3  7.69E−254 0.435214924 1 1  1.91E−249 A96 Apoe Cdo12  1.76E−207 0.535977967 0.998 0.957  4.37E−203 A96 Cdo1 Mat1a3  8.71E−192 0.506975785 1 0.976  2.16E−187 A96 Mat1a Chchd103  3.76E−191 0.565314195 0.994 0.932  9.34E−187 A96 Chchd10 Ces1d3  1.37E−181 0.655727144 0.977 0.851  3.39E−177 A96 Ces1d Apoh2  2.09E−169 0.393709699 0.998 0.982  5.20E−165 A96 Apoh Ttpa1  6.68E−154 0.524445158 0.98 0.887  1.66E−149 A96 Ttpa Ttr2  2.48E−153 0.326050936 1 0.999  6.15E−149 A96 Ttr Hmgcs22  1.07E−147 0.394397485 0.996 0.973  2.66E−143 A96 Hmgcs2 Cyp8b13  2.40E−140 0.659833251 0.897 0.633  5.96E−136 A96 Cyp8b1 Ces1c2  4.90E−137 0.356546281 1 0.986  1.22E−132 A96 Ces1e Cyp3a113  1.05E−126 0.384595952 0.999 0.997  2.60E−122 A96 Cyp3a11 Rbp41  5.06E−125 0.310027462 1 0.996  1.26E−120 A96 Rbp4 Retsat3  2.48E−120 0.5525706 0.957 0.774  6.16E−116 A96 Retsat Ubc2  1.57E−116 0.480123165 0.968 0.854  3.90E−112 A96 Ubc Rdh72  1.30E−109 0.351444842 0.995 0.959  3.22E−105 A96 Rdh7 Cyp3a252  1.47E−109 0.421753505 0.981 0.887  3.66E−105 A96 Cyp3a25 Slco1b22  1.65E−109 0.556869709 0.998 0.932  4.10E−105 A96 Slco1b2 Cyp2c293  1.10E−108 0.755089243 0.962 0.817  2.74E−104 A96 Cyp2c29 Acsl12  1.94E−103 0.438089942 0.977 0.879 4.82E−99 A96 Acsl1 Cyp2c541 2.26E−99 0.556201457 0.86 0.619 5.61E−95 A96 Cyp2c54 Atp5h3 2.14E−97 0.467241244 0.848 0.623 5.32E−93 A96 Atp5h Fth11 4.12E−97 0.313702253 0.993 0.978 1.02E−92 A96 Fth1 Apoc33 2.02E−93 0.303331054 1 0.983 5.01E−89 A96 Apoc3 Ugt2b53 4.35E−89 0.339957413 0.986 0.94 1.08E−84 A96 Ugt2b5 Creg11 4.42E−89 0.374731894 0.985 0.908 1.10E−84 A96 Creg1 Cyp2c501 2.42E−88 0.50581129 0.943 0.789 6.01E−84 A96 Cyp2c50 Acaa1b2 4.73E−88 0.414844819 0.986 0.887 1.17E−83 A96 Acaa1b Apoc43 9.68E−87 0.310736478 0.998 0.974 2.40E−82 A96 Apoc4 Acbd52 1.19E−85 0.452425437 0.87 0.712 2.96E−81 A96 Acbd5 Sod11 2.96E−84 0.305519465 0.999 0.977 7.35E−80 A96 Sod1 Slc27a21 3.51E−84 0.327297475 0.988 0.945 8.71E−80 A96 Slc27a2 Amy12 2.18E−82 0.463903122 0.831 0.656 5.41E−78 A96 Amy1 Cyp2c372 8.65E−78 0.601371289 0.71 0.425 2.15E−73 A96 Cyp2c37 Crot1 2.32E−77 0.308615744 0.989 0.952 5.77E−73 A96 Crot Nr1i33 3.31E−76 0.4562148 0.625 0.352 8.22E−72 A96 Nr1i3 Sult1d12 6.18E−76 0.483383193 0.855 0.677 1.53E−71 A96 Sult1d1 Ppp2r5a 1.50E−75 0.458718371 0.764 0.569 3.73E−71 A96 Ppp2r5a Hhex 1.71E−75 0.418536303 0.543 0.286 4.25E−71 A96 Hhex Hamp3 3.47E−74 0.478368592 0.92 0.793 8.61E−70 A96 Hamp Chpt1 7.37E−74 0.430823819 0.848 0.677 1.83E−69 A96 Chpt1 Clpx1 1.31E−73 0.408117525 0.884 0.751 3.25E−69 A96 Clpx Cyp2b101 3.02E−73 0.335177862 0.68 0.351 7.50E−69 A96 Cyp2b10 Abcb41 1.73E−72 0.424225528 0.878 0.706 4.31E−68 A96 Abcb4 Aldh3a22 3.15E−72 0.604174759 0.687 0.432 7.81E−68 A96 Aldh3a2 Cox6a13 2.09E−71 0.35746573 0.943 0.853 5.18E−67 A96 Cox6a1 Pon11 4.31E−71 0.391882148 0.965 0.879 1.07E−66 A96 Pon1 Insig22 1.33E−70 0.368288039 0.928 0.801 3.31E−66 A96 Insig2 Cth1 3.72E−70 0.390224363 0.944 0.823 9.23E−66 A96 Cth Atp5k2 1.24E−68 0.397998927 0.837 0.677 3.08E−64 A96 Atp5k Ndrg22 2.58E−68 0.279303859 0.985 0.946 6.42E−64 A96 Ndrg2 Mettl7b1 1.30E−67 0.330779976 0.949 0.884 3.24E−63 A96 Mettl7b Mgst11 5.26E−65 0.251672309 1 0.995 1.31E−60 A96 Mgst1 Snord1182 2.18E−63 0.439343487 0.564 0.324 5.41E−59 A96 Snord118 Ephx22 1.06E−62 0.284030828 0.968 0.908 2.63E−58 A96 Ephx2 Bhmt1 2.63E−62 0.268226692 0.991 0.947 6.54E−58 A96 Bhmt Cyb53 3.62E−62 0.275263191 1 0.977 9.00E−58 A96 Cyb5 Rps27l3 4.23E−62 0.345949131 0.909 0.778 1.05E−57 A96 Rps27l Hmgcl1 1.14E−61 0.364377659 0.871 0.722 2.83E−57 A96 Hmgcl Gsta21 7.73E−60 0.39758707 0.522 0.301 1.92E−55 A96 Gsta2 Sc4mol1 1.00E−59 0.397503269 0.781 0.603 2.49E−55 A96 Sc4mol Pex11a 1.54E−59 0.461213321 0.7 0.487 3.81E−55 A96 Pex11a Hspa83 1.87E−57 0.334752875 0.905 0.782 4.66E−53 A96 Hspa8 Ube2r22 3.50E−57 0.373950286 0.747 0.565 8.69E−53 A96 Ube2r2 Lipa2 4.84E−56 0.364686822 0.791 0.651 1.20E−51 A96 Lipa Csad2 7.79E−55 0.455104263 0.843 0.641 1.93E−50 A96 Csad Acat11 7.95E−55 0.330094254 0.917 0.837 1.97E−50 A96 Acat1 Baat2 8.13E−55 0.351413298 0.862 0.747 2.02E−50 A96 Baat Tmem56 3.20E−54 0.357155569 0.812 0.642 7.96E−50 A96 Tmem56 Slc10a12 4.49E−53 0.309448919 0.936 0.847 1.12E−48 A96 Slc10a1 Acot11 4.63E−53 0.35120599 0.459 0.24 1.15E−48 A96 Acot1 Bnip33 6.74E−53 0.396644557 0.716 0.534 1.67E−48 A96 Bnip3 Aldh1a11 1.69E−52 0.290873161 0.994 0.953 4.19E−48 A96 Aldh1a1 Ahcy2 3.19E−52 0.276868815 0.934 0.864 7.91E−48 A96 Ahcy Gstt31 4.66E−52 0.35168382 0.541 0.323 1.16E−47 A96 Gstt3 Sec14l22 2.20E−51 0.283306885 0.939 0.849 5.47E−47 A96 Sec14l2 Gas52 1.11E−50 0.359650606 0.68 0.498 2.76E−46 A96 Gas5 Gabarapl1 7.02E−50 0.3228272 0.881 0.777 1.74E−45 A96 Gabarapl1 Decr21 7.27E−49 0.330020285 0.813 0.664 1.81E−44 A96 Decr2 Ndufa71 5.85E−48 0.315860633 0.818 0.68 1.45E−43 A96 Ndufa7 Aldh9a11 3.79E−47 0.300984838 0.884 0.784 9.42E−43 A96 Aldh9a1 Acot4 1.70E−45 0.256272851 0.328 0.149 4.23E−41 A96 Acot4 Cyp2e12 2.08E−45 0.467377427 0.93 0.811 5.16E−41 A96 Cyp2e1 Hsd17b102 3.65E−45 0.331127034 0.841 0.69 9.06E−41 A96 Hsd17b10 Gyk1 4.15E−45 0.328560139 0.616 0.441 1.03E−40 A96 Gyk Asl2 4.43E−45 0.29391729 0.896 0.806 1.10E−40 A96 Asl Slco1a41 9.51E−45 0.35964429 0.507 0.311 2.36E−40 A96 Slco1a4 Akr1d12 1.27E−44 0.320114687 0.721 0.56 3.16E−40 A96 Akr1d1 Abcc31 1.93E−44 0.332981906 0.733 0.561 4.80E−40 A96 Abcc3 Kif1b1 2.02E−44 0.335011009 0.686 0.499 5.03E−40 A96 Kif1b Sord2 2.10E−44 0.260491087 0.969 0.917 5.21E−40 A96 Sord Sult1a12 2.75E−44 0.301146751 0.881 0.767 6.82E−40 A96 Sult1a1 Dpys1 9.36E−44 0.288671839 0.824 0.689 2.32E−39 A96 Dpys Eif52 1.10E−43 0.271819491 0.879 0.748 2.73E−39 A96 Eif5 G0s22 1.78E−43 0.311001159 0.525 0.315 4.41E−39 A96 G0s2 Ctage51 2.81E−43 0.312935082 0.837 0.703 6.98E−39 A96 Ctage5 0610005C13Rik2 4.35E−43 0.300794029 0.816 0.668 1.08E−38 A96 0610005C13Rik Hmgcs11 4.61E−43 0.301665601 0.858 0.716 1.14E−38 A96 Hmgcs1 Ugp22 7.52E−42 0.303666951 0.858 0.753 1.87E−37 A96 Ugp2 Mia31 8.38E−42 0.315853543 0.81 0.647 2.08E−37 A96 Mia3 Ndufb92 1.14E−41 0.269298954 0.951 0.859 2.83E−37 A96 Ndufb9 Pbld12 1.54E−41 0.307893385 0.723 0.575 3.82E−37 A96 Pbld1 Serpinf11 2.07E−41 0.262905272 0.934 0.861 5.15E−37 A96 Serpinf1 Gm49522 2.95E−41 0.320671041 0.663 0.507 7.34E−37 A96 Gm4952 Hpgd1 3.39E−41 0.349307092 0.588 0.404 8.42E−37 A96 Hpgd Cyp7a12 3.62E−41 0.311335446 0.398 0.205 8.98E−37 A96 Cyp7a1 Cd1d11 6.77E−41 0.301788074 0.747 0.615 1.68E−36 A96 Cd1d1 Prlr 9.98E−41 0.301923874 0.574 0.38 2.48E−36 A96 Prlr Rdh16 1.14E−40 0.351901508 0.494 0.306 2.82E−36 A96 Rdh16 Cox5a2 2.78E−40 0.296306496 0.813 0.713 6.92E−36 A96 Cox5a Gadd45b 9.36E−40 0.342036421 0.452 0.264 2.32E−35 A96 Gadd45b Rdx2 2.27E−39 0.281003468 0.824 0.683 5.64E−35 A96 Rdx Slc25a201 2.93E−39 0.295187748 0.671 0.53 7.28E−35 A96 Slc25a20 Decr13 5.27E−39 0.300003168 0.808 0.694 1.31E−34 A96 Decr1 Slc40a12 8.03E−39 0.286363927 0.551 0.367 1.99E−34 A96 Slc40a1 Cxcl121 1.08E−38 0.300468634 0.635 0.477 2.69E−34 A96 Cxcl12 Tob11 1.08E−38 0.301044665 0.649 0.492 2.69E−34 A96 Tob1 Ces1f1 1.95E−38 0.278175079 0.895 0.793 4.83E−34 A96 Ces1f Arl4a 4.10E−38 0.293413307 0.517 0.333 1.02E−33 A96 Arl4a Tsc22d3 4.12E−38 0.318115028 0.534 0.353 1.02E−33 A96 Tsc22d3 Apoc21 5.51E−38 0.287194802 0.901 0.828 1.37E−33 A96 Apoc2 Cyp2c681 6.33E−38 0.311687849 0.695 0.524 1.57E−33 A96 Cyp2c68 Slc4a41 4.04E−37 0.29162163 0.609 0.43 1.00E−32 A96 Slc4a4 Gclm 4.44E−37 0.269048382 0.865 0.751 1.10E−32 A96 Gclm Hsd17b7 5.55E−37 0.30226456 0.56 0.384 1.38E−32 A96 Hsd17b7 Ech12 8.48E−37 0.250879529 0.917 0.814 2.10E−32 A96 Ech1 Acot121 1.14E−36 0.280173953 0.65 0.477 2.83E−32 A96 Acot12 Etfdh 2.18E−36 0.27680923 0.811 0.707 5.40E−32 A96 Etfdh Ndufa31 2.39E−36 0.276535456 0.737 0.602 5.93E−32 A96 Ndufa3 Tgoln11 2.68E−36 0.296779403 0.756 0.631 6.66E−32 A96 Tgoln1 Lcat2 3.69E−36 0.251857226 0.886 0.805 9.16E−32 A96 Lcat Ephx11 3.81E−36 0.252026139 0.879 0.773 9.45E−32 A96 Ephx1 Zfp911 8.05E−36 0.325520389 0.693 0.547 2.00E−31 A96 Zfp91 Ndufb23 1.78E−35 0.300482948 0.731 0.599 4.43E−31 A96 Ndufb2 D4Wsu53e 3.13E−35 0.292450804 0.597 0.419 7.76E−31 A96 D4Wsu53e Apol7a1 5.39E−35 0.302856549 0.559 0.392 1.34E−30 A96 Apol7a Mtdh1 1.22E−34 0.283760224 0.649 0.492 3.03E−30 A96 Mtdh Cisd11 2.63E−34 0.28202591 0.781 0.674 6.53E−30 A96 Cisd1 Slc25a102 6.62E−34 0.260509641 0.701 0.552 1.64E−29 A96 Slc25a10 Sdhc1 8.91E−34 0.272202687 0.76 0.66 2.21E−29 A96 Sdhc Aqp91 1.11E−33 0.290066048 0.801 0.679 2.76E−29 A96 Aqp9 Crls1 1.54E−33 0.255032135 0.447 0.281 3.83E−29 A96 Crls1 Aplp2 2.37E−33 0.256928992 0.826 0.696 5.89E−29 A96 Aplp2 Tmed51 4.31E−33 0.256258347 0.714 0.572 1.07E−28 A96 Tmed5 Ces1e1 1.15E−32 0.310850144 0.71 0.581 2.85E−28 A96 Ces1e Dhdh1 6.97E−32 0.259307598 0.734 0.62 1.73E−27 A96 Dhdh Nfe2l2 1.68E−31 0.251281214 0.465 0.294 4.17E−27 A96 Nfe2l2 Cpeb4 3.46E−31 0.299434499 0.527 0.371 8.60E−27 A96 Cpeb4 8430408G22Rik1 3.96E−31 0.277441955 0.559 0.389 9.83E−27 A96 8430408G22Rik Cd36 4.36E−31 0.278212926 0.299 0.153 1.08E−26 A96 Cd36 Prkd32 4.40E−31 0.259284079 0.682 0.541 1.09E−26 A96 Prkd3 Brap1 1.04E−30 0.25715186 0.642 0.497 2.59E−26 A96 Brap Mocs21 1.07E−30 0.26658769 0.737 0.615 2.66E−26 A96 Mocs2 Agpat6 1.18E−30 0.275279281 0.743 0.61 2.93E−26 A96 Agpat6 Tmem106b 1.28E−30 0.260426336 0.727 0.602 3.17E−26 A96 Tmem106b Pabpc12 1.03E−29 0.252666197 0.766 0.655 2.55E−25 A96 Pabpc1 D17Wsu92e1 1.06E−29 0.257998282 0.771 0.653 2.62E−25 A96 D17Wsu92e Cyp2c442 1.54E−29 0.264049939 0.828 0.728 3.82E−25 A96 Cyp2c44 Dcxr3 1.66E−29 0.252198764 0.735 0.6 4.13E−25 A96 Dcxr Ptp4a2 4.47E−29 0.263379468 0.691 0.573 1.11E−24 A96 Ptp4a2 Sdhd2 4.97E−29 0.260964394 0.775 0.664 1.23E−24 A96 Sdhd Ehhadh1 2.37E−28 0.254528118 0.78 0.673 5.88E−24 A96 Ehhadh Pdk1 3.43E−28 0.255751279 0.438 0.283 8.51E−24 A96 Pdk1 Cyp2a53 8.31E−28 0.346687234 0.581 0.389 2.06E−23 A96 Cyp2a5 Cebpb3 4.85E−27 0.251454788 0.585 0.443 1.20E−22 A96 Cebpb Usmg52 7.28E−27 0.256460761 0.59 0.443 1.81E−22 A96 Usmg5 Rgn2 1.30E−26 0.290981568 0.899 0.808 3.23E−22 A96 Rgn Cede107 7.35E−26 0.26255392 0.59 0.458 1.82E−21 A96 Cede107 Fmo1 3.25E−25 0.253513023 0.606 0.456 8.06E−21 A96 Fmo1 Etnppl3 1.26E−24 0.410971098 0.677 0.569 3.13E−20 A96 Etnppl Hamp2 5.46E−24 0.259654924 0.203 0.093 1.35E−19 A96 Hamp2 Cpox1 1.04E−21 0.25616093 0.634 0.522 2.58E−17 A96 Cpox Oat2 3.84E−20 0.321311893 0.653 0.508 9.53E−16 A96 Oat Mt24 0 1.789997157 1 0.555 0 PHX3 Mt2 Mt14 0 1.628319565 1 0.709 0 PHX3 Mt1 Steap44 0 1.546860615 0.973 0.366 0 PHX3 Steap4 Lpin13 0 1.189493717 0.94 0.39 0 PHX3 Lpin1 Serpina3n3 0 1.186862923 0.992 0.723 0 PHX3 Serpina3n Thrsp3 0 1.107456378 0.98 0.578 0 PHX3 Thrsp Cxcl13 0 1.09269701 0.919 0.364 0 PHX3 Cxcl1 Igfbp13 0 1.083068625 0.99 0.73 0 PHX3 Igfbp1 Tacc22 0 0.799081935 0.707 0.148 0 PHX3 Tacc2 Scd11 0 0.743251417 0.998 0.936 0 PHX3 Scd1 Fam134b1 0 0.727776721 0.876 0.482 0 PHX3 Fam134b St3gal53 0 0.726028159 0.915 0.574 0 PHX3 St3gal5 Il1r13 0 0.711336628 0.8 0.322 0 PHX3 Il1r1 B3galt12 0 0.705093027 0.634 0.225 0 PHX3 B3galt1 H3f3b3 0 0.694554678 0.831 0.454 0 PHX3 H3f3b Nnmt3 0 0.668908642 0.97 0.767 0 PHX3 Nnmt Slc38a2 0 0.666231739 0.874 0.49 0 PHX3 Slc38a2 Tat2 0 0.643729389 0.998 0.929 0 PHX3 Tat n-R5-8s13 0 0.641983104 0.805 0.246 0 PHX3 n-R5-8s1 Slc39a142 0 0.580960968 0.849 0.469 0 PHX3 Slc39a14 Fkbp52 0 0.562874909 0.665 0.218 0 PHX3 Fkbp5 Plin23 0 0.560892991 0.952 0.739 0 PHX3 Plin2 Slc25a472 0 0.556992763 0.994 0.905 0 PHX3 Slc25a47 Gm246013 0 0.531358312 0.661 0.173 0 PHX3 Gm24601 Serpina1e1 0 0.510250179 1 0.994 0 PHX3 Serpina1e Cldn14 0 0.480249207 0.505 0.109 0 PHX3 Cldn14 Fga3 0 0.479585344 1 0.996 0 PHX3 Fga Fgg3 0 0.468687867 1 0.995 0 PHX3 Fgg Acox12 0 0.456568318 0.998 0.962 0 PHX3 Acox1 Rcan11 0 0.434158745 0.522 0.133 0 PHX3 Rcan1 Aldob1 0 0.415637015 1 0.996 0 PHX3 Aldob Fgb3 0 0.400821016 1 0.999 0 PHX3 Fgb Pfkfb3 0 0.388386728 0.421 0.063 0 PHX3 Pfkfb3 Fbf1 0 0.292192664 0.336 0.034 0 PHX3 Fbf1 Rapgef42  4.60E−302 0.581053171 0.836 0.461  1.14E−297 PHX3 Rapgef4 Upp22  6.10E−292 0.572267247 0.934 0.645  1.52E−287 PHX3 Upp2 Arhgef26  3.60E−291 0.49916866 0.67 0.272  8.95E−287 PHX3 Arhgef26 Aass  2.84E−286 0.585116267 0.965 0.756  7.05E−282 PHX3 Aass Gadd45g2  1.61E−283 0.563511755 0.899 0.56  4.01E−279 PHX3 Gadd45g Fmo5  3.25E−279 0.495494591 0.991 0.879  8.06E−275 PHX3 Fmo5 Bcl3  1.59E−278 0.366999466 0.479 0.134  3.94E−274 PHX3 Bcl3 Tiparp1  3.77E−277 0.440747263 0.485 0.14  9.36E−273 PHX3 Tiparp Saa43  3.26E−273 0.499433314 0.981 0.79  8.10E−269 PHX3 Saa4 Txnip  8.19E−267 0.534615839 0.741 0.346  2.03E−262 PHX3 Txnip Errfi1  9.98E−264 0.409765728 0.998 0.928  2.48E−259 PHX3 Errfi1 Scp22  4.34E−260 0.350885679 0.997 0.972  1.08E−255 PHX3 Scp2 Snx10  1.61E−256 0.472894384 0.63 0.263  3.99E−252 PHX3 Snx10 Gpcpd11  3.99E−254 0.553228383 0.778 0.419  9.92E−250 PHX3 Gpcpd1 Lcn24  5.86E−253 0.318374231 0.815 0.323  1.46E−248 PHX3 Lcn2 Btg21  1.73E−250 0.577772828 0.708 0.344  4.30E−246 PHX3 Btg2 2010003K11Rik1  5.13E−243 0.306670297 0.412 0.107  1.27E−238 PHX3 2010003K11Rik Serpina3m1  1.19E−239 0.488987274 0.961 0.784  2.95E−235 PHX3 Serpina3m Gstp13  2.19E−238 0.482301792 0.962 0.741  5.45E−234 PHX3 Gstp1 Etnk21  3.85E−238 0.519747051 0.918 0.685  9.57E−234 PHX3 Etnk2 Plin52  2.34E−236 0.455223479 0.736 0.361  5.81E−232 PHX3 Plin5 Bach11  4.06E−233 0.423068365 0.589 0.237  1.01E−228 PHX3 Bach1 Tdo2  3.68E−231 0.319972551 0.999 0.981  9.15E−227 PHX3 Tdo2 Tifa  2.38E−230 0.311085748 0.393 0.1  5.92E−226 PHX3 Tifa Itih43  1.33E−228 0.354098265 0.999 0.968  3.30E−224 PHX3 Itih4 Fam35a  2.66E−225 0.437093621 0.642 0.292  6.61E−221 PHX3 Fam35a Plk32  9.69E−225 0.430480294 0.644 0.287  2.41E−220 PHX3 Plk3 Hspb82  2.27E−224 0.492739021 0.914 0.662  5.63E−220 PHX3 Hspb8 Ptp4a1  2.29E−218 0.364094864 0.528 0.2  5.68E−214 PHX3 Ptp4a1 Xbp12  4.38E−212 0.448896235 0.89 0.611  1.09E−207 PHX3 Xbp1 Slc7a2  3.94E−210 0.446001839 0.964 0.762  9.78E−206 PHX3 Slc7a2 Sds3  2.76E−209 0.764967866 0.868 0.592  6.84E−205 PHX3 Sds Gpt21  3.87E−209 0.43436454 0.949 0.752  9.60E−205 PHX3 Gpt2 Arg1  1.02E−200 0.315251526 1 0.978  2.54E−196 PHX3 Arg1 Rnf103  7.01E−200 0.429306898 0.701 0.376  1.74E−195 PHX3 Rnf103 Apoa52  2.12E−195 0.335415384 0.999 0.952  5.27E−191 PHX3 Apoa5 Slc25a25  1.00E−194 0.424727464 0.945 0.745  2.49E−190 PHX3 Slc25a25 Klf10  1.02E−194 0.26769517 0.388 0.114  2.53E−190 PHX3 Klf10 Fh11  4.84E−194 0.45501042 0.915 0.685  1.20E−189 PHX3 Fh1 Trib1  7.34E−194 0.467455716 0.705 0.386  1.82E−189 PHX3 Trib1 Atf3  2.03E−192 0.484651606 0.56 0.24  5.04E−188 PHX3 Atf3 Gjb22  1.51E−188 0.429397446 0.901 0.661  3.76E−184 PHX3 Gjb2 Got11  1.69E−188 0.48064162 0.866 0.618  4.20E−184 PHX3 Got1 1810055G02Rik  1.32E−186 0.352031321 0.528 0.217  3.27E−182 PHX3 1810055G02Rik Id2  2.54E−186 0.465018314 0.826 0.555  6.30E−182 PHX3 Id2 Egfr3  6.93E−185 0.392521443 0.989 0.837  1.72E−180 PHX3 Egfr Rgs162  1.91E−184 0.362782533 0.482 0.174  4.73E−180 PHX3 Rgs16 Mtss11  4.80E−183 0.438122599 0.812 0.523  1.19E−178 PHX3 Mtss1 Rhob  2.92E−182 0.314794887 0.4 0.13  7.25E−178 PHX3 Rhob Junb  9.45E−182 0.446083855 0.788 0.495  2.35E−177 PHX3 Junb Egr12  2.29E−180 0.492150366 0.79 0.491  5.68E−176 PHX3 Egr1 Mbd1  9.76E−179 0.333504242 0.507 0.202  2.42E−174 PHX3 Mbd1 Pck11  2.20E−178 0.304952819 0.999 0.975  5.47E−174 PHX3 Pck1 Serpina103  1.39E−177 0.394340765 0.934 0.731  3.45E−173 PHX3 Serpina10 Slc25a51  8.62E−177 0.328040909 0.522 0.218  2.14E−172 PHX3 Slc25a51 Klf61  1.14E−176 0.258557871 0.346 0.097  2.82E−172 PHX3 Klf6 Cdkn1a3  6.07E−174 0.321419697 0.572 0.245  1.51E−169 PHX3 Cdkn1a Shb  6.63E−172 0.354830541 0.589 0.281  1.65E−167 PHX3 Shb Hnf4a1  3.33E−169 0.369123652 0.969 0.806  8.26E−165 PHX3 Hnf4a Jun  1.45E−168 0.455833119 0.864 0.61  3.60E−164 PHX3 Jun Dak  3.89E−168 0.429081642 0.867 0.599  9.65E−164 PHX3 Dak Mup10  1.70E−164 0.315514103 0.965 0.779  4.21E−160 PHX3 Mup10 Fasn  1.97E−164 0.393405386 0.719 0.395  4.90E−160 PHX3 Fasn Slc25a22  3.24E−162 0.348459422 0.649 0.339  8.04E−158 PHX3 Slc25a22 B4galt1  3.41E−161 0.277865586 0.494 0.203  8.46E−157 PHX3 B4galt1 Actb3  2.10E−156 0.283891315 0.99 0.906  5.20E−152 PHX3 Actb Cyp4a12a2  3.54E−156 0.403038241 0.823 0.512  8.80E−152 PHX3 Cyp4a12a Lrg11  4.69E−155 0.317155413 0.981 0.837  1.16E−150 PHX3 Lrg1 Elovl6  7.53E−153 0.369426318 0.553 0.268  1.87E−148 PHX3 Elovl6 Nfil31  4.61E−152 0.345982344 0.617 0.317  1.14E−147 PHX3 Nfil3 G6pc2  3.85E−151 0.423823035 0.948 0.74  9.56E−147 PHX3 G6pc Myo1e1  5.05E−151 0.313552851 0.551 0.251  1.25E−146 PHX3 Myo1e Ivns1abp  7.63E−151 0.358642904 0.688 0.394  1.89E−146 PHX3 Ivns1abp Uox1  5.40E−149 0.269119908 0.998 0.966  1.34E−144 PHX3 Uox Sephs23  2.80E−146 0.327490234 0.974 0.817  6.95E−142 PHX3 Sephs2 Ier2  8.72E−146 0.427074433 0.763 0.509  2.17E−141 PHX3 Ier2 B2m2  9.57E−146 0.274069023 0.997 0.953  2.38E−141 PHX3 B2m Jmjd1c1  2.06E−144 0.322197078 0.516 0.238  5.11E−140 PHX3 Jmjd1c Sdc41  2.93E−141 0.29285071 0.986 0.895  7.26E−137 PHX3 Sdc4 Atp1b1  1.89E−138 0.34781274 0.567 0.293  4.69E−134 PHX3 Atp1b1 Selenbp23  4.97E−138 0.374671601 0.986 0.828  1.23E−133 PHX3 Selenbp2 Ccnl1  1.61E−137 0.31921767 0.526 0.253  3.99E−133 PHX3 Ccnl1 Mfsd2a3  5.03E−136 0.28900787 0.563 0.263  1.25E−131 PHX3 Mfsd2a Id31  3.10E−132 0.450224629 0.688 0.421  7.70E−128 PHX3 Id3 Abca13  3.84E−131 0.324806561 0.756 0.465  9.53E−127 PHX3 Abca1 Ddx3x1  1.66E−128 0.348123451 0.823 0.578  4.13E−124 PHX3 Ddx3x Aox33  4.73E−128 0.334555042 0.989 0.876  1.18E−123 PHX3 Aox3 Tns11  2.48E−121 0.270591692 0.524 0.257  6.16E−117 PHX3 Tns1 Slco1a11  7.28E−121 0.323170693 0.927 0.71  1.81E−116 PHX3 Slco1a1 Pik3r1  6.11E−119 0.299120271 0.577 0.313  1.52E−114 PHX3 Pik3r1 Gfra1  2.01E−118 0.31861648 0.835 0.584  4.99E−114 PHX3 Gfra1 Atl2  8.16E−117 0.288947906 0.674 0.404  2.03E−112 PHX3 Atl2 Zfp36  1.13E−115 0.375886126 0.776 0.543  2.82E−111 PHX3 Zfp36 Gck  6.80E−113 0.272963666 0.557 0.289  1.69E−108 PHX3 Gck Ulk1  1.04E−111 0.255629811 0.499 0.247  2.58E−107 PHX3 Ulk1 Bhlhe40  2.78E−111 0.272247091 0.628 0.351  6.90E−107 PHX3 Bhlhe40 Serpina122  3.41E−107 0.343116487 0.648 0.372  8.46E−103 PHX3 Serpina12 Stat32  2.75E−106 0.254119857 0.701 0.431  6.83E−102 PHX3 Stat3 Litaf  1.58E−105 0.282863512 0.603 0.361  3.93E−101 PHX3 Litaf Fos  9.31E−103 0.379607371 0.785 0.559 2.31E−98 PHX3 Fos Csad3  2.57E−102 0.409237969 0.872 0.611 6.38E−98 PHX3 Csad Slc25a15 1.32E−99 0.287179656 0.931 0.782 3.27E−95 PHX3 Slc25a15 Cpt1a 3.31E−96 0.287909766 0.894 0.695 8.23E−92 PHX3 Cpt1a Cyp2f21 1.47E−94 0.355492212 0.965 0.788 3.66E−90 PHX3 Cyp2f2 Pim32 1.63E−93 0.292474208 0.764 0.54 4.04E−89 PHX3 Pim3 Pnpla74 8.45E−93 0.269572352 0.807 0.571 2.10E−88 PHX3 Pnpla7 Acly3 1.33E−90 0.279828458 0.715 0.471 3.30E−86 PHX3 Acly Ifitm33 4.94E−89 0.257336347 0.958 0.819 1.23E−84 PHX3 Ifitm3 Angptl41 7.69E−89 0.287033468 0.838 0.637 1.91E−84 PHX3 Angptl4 Pklr 8.66E−88 0.258258018 0.624 0.385 2.15E−83 PHX3 Pklr Eci21 1.78E−87 0.251237147 0.896 0.699 4.41E−83 PHX3 Eci2 Me1 3.42E−87 0.256971177 0.699 0.45 8.49E−83 PHX3 Me1 Elovl5 9.27E−86 0.284139128 0.863 0.635 2.30E−81 PHX3 Elovl5 Enpp2 3.09E−85 0.258210814 0.635 0.402 7.68E−81 PHX3 Enpp2 Jak11 1.56E−81 0.253798387 0.648 0.415 3.88E−77 PHX3 Jak1 Gls2 3.38E−77 0.286724421 0.868 0.648 8.39E−73 PHX3 Gls2 Rcl1 3.70E−76 0.262666169 0.734 0.532 9.20E−72 PHX3 Rcl1 Saa35 0 2.175493617 0.629 0.098 0 PHX48 Saa3 Saa24 0 2.173589396 0.995 0.473 0 PHX48 Saa2 Saa14 0 2.03134899 0.999 0.722 0 PHX48 Saa1 Orm25 0 1.9624582 0.882 0.244 0 PHX48 Orm2 Apcs3 0 1.668765328 0.922 0.677 0 PHX48 Apcs Orm13 0 1.510438466 0.997 0.962 0 PHX48 Orm1 Lcn25 0 1.392839951 0.862 0.363 0 PHX48 Lcn2 Hpx3 0 1.146101117 1 0.998 0 PHX48 Hpx Hp3 0 1.114046301 1 0.999 0 PHX48 Hp Fgl13 0 1.043568641 0.967 0.872 0 PHX48 Fgl1 Itih44  1.13E−213 0.645979807 0.99 0.972  2.82E−209 PHX48 Itih4 Trf1  1.02E−212 0.482924139 0.997 0.998  2.54E−208 PHX48 Trf Itih32  1.73E−208 0.781133024 0.963 0.938  4.29E−204 PHX48 Itih3 Csf2ra  4.36E−198 0.338511697 0.158 0.009  1.08E−193 PHX48 Csf2ra C3  1.57E−185 0.56180364 0.998 0.995  3.91E−181 PHX48 C3 Gm269244  5.19E−162 0.652363116 1 1  1.29E−157 PHX48 Gm26924 Fam25c3  1.03E−139 0.967401342 0.653 0.383  2.56E−135 PHX48 Fam25c D17H6S56E-5  3.62E−121 0.530503537 0.152 0.018  8.99E−117 PHX48 D17H6S56E-5 Hmgcs13  4.47E−108 0.781596583 0.819 0.717  1.11E−103 PHX48 Hmgcs1 Ambp 3.32E−95 0.306730872 0.995 0.994 8.25E−91 PHX48 Ambp Rnase42 1.43E−87 0.535044621 0.933 0.935 3.56E−83 PHX48 Rnase4 Lrg12 3.00E−84 0.490737188 0.905 0.857 7.46E−80 PHX48 Lrg1 Apoa44 1.51E−81 0.809620465 0.658 0.483 3.75E−77 PHX48 Apoa4 Dhcr24 1.13E−73 0.513450385 0.862 0.863 2.81E−69 PHX48 Dhcr24 Prtn3 1.78E−73 0.258105361 0.2 0.051 4.43E−69 PHX48 Prtn3 Gstm34 2.36E−71 1.042882879 0.543 0.347 5.86E−67 PHX48 Gstm3 1100001G20Rik2 8.36E−71 0.349146589 0.982 0.98 2.08E−66 PHX48 1100001G20Rik Ang2 9.46E−68 0.554661583 0.773 0.72 2.35E−63 PHX48 Ang Fga4 2.42E−66 0.410993472 0.992 0.998 6.01E−62 PHX48 Fga C4bp1 6.90E−60 0.365491689 0.852 0.854 1.71E−55 PHX48 C4bp Cfh2 1.21E−55 0.346063736 0.911 0.934 3.01E−51 PHX48 Cfh Tmem176a1 2.65E−53 0.502002681 0.637 0.55 6.57E−49 PHX48 Tmem176a Cp1 8.84E−53 0.346340984 0.952 0.967 2.20E−48 PHX48 Cp Rpl412 2.41E−52 0.516910533 0.528 0.355 5.98E−48 PHX48 Rpl41 Nnmt4 4.00E−52 0.431614865 0.825 0.799 9.92E−48 PHX48 Nnmt Gstm2 5.13E−52 0.49759485 0.345 0.17 1.27E−47 PHX48 Gstm2 Hsp90ab1 1.68E−51 0.300059266 0.923 0.951 4.16E−47 PHX48 Hsp90ab1 Tmem176b1 6.17E−51 0.43901744 0.744 0.717 1.53E−46 PHX48 Tmem176b Dbi1 1.25E−49 0.325825837 0.969 0.972 3.11E−45 PHX48 Dbi Serpina104 4.43E−48 0.509521298 0.772 0.765 1.10E−43 PHX48 Serpina10 Cyp7a13 5.38E−48 0.694022545 0.372 0.205 1.34E−43 PHX48 Cyp7a1 Marco 4.74E−47 0.26221596 0.106 0.023 1.18E−42 PHX48 Marco Isyna1 9.14E−47 0.270858578 0.219 0.084 2.27E−42 PHX48 Isyna1 Ccnd1 3.60E−45 0.325431422 0.218 0.084 8.93E−41 PHX48 Ccnd1 Fgb4 1.38E−44 0.286867229 0.999 1 3.42E−40 PHX48 Fgb Cd5l1 3.26E−43 0.339742048 0.199 0.071 8.09E−39 PHX48 Cd5l Cd3021 5.51E−43 0.359660787 0.864 0.885 1.37E−38 PHX48 Cd302 Ifitm22 1.71E−41 0.463721039 0.532 0.417 4.26E−37 PHX48 Ifitm2 Fgg4 3.83E−38 0.293846068 0.996 0.996 9.52E−34 PHX48 Fgg C1qb1 6.74E−30 0.27028615 0.163 0.064 1.67E−25 PHX48 C1qb Alas12 1.49E−29 0.357004678 0.749 0.766 3.70E−25 PHX48 Alas1 Cyp51 3.15E−26 0.428575287 0.67 0.678 7.82E−22 PHX48 Cyp51 Rbp1 1.44E−25 0.312016246 0.264 0.148 3.58E−21 PHX48 Rbp1 Gas6 4.77E−25 0.286153321 0.215 0.111 1.19E−20 PHX48 Gas6 BC048546 5.45E−22 0.273479948 0.265 0.159 1.35E−17 PHX48 BC048546 n-R5-8s14 1.33E−21 0.48615855 0.464 0.33 3.29E−17 PHX48 n-R5-8s1 Dynll1 2.25E−21 0.302178838 0.283 0.181 5.60E−17 PHX48 Dynll1 Gm12744 9.64E−21 0.289497387 0.231 0.134 2.39E−16 PHX48 Gm12744 Acnat2 5.19E−20 0.272696647 0.252 0.154 1.29E−15 PHX48 Acnat2 Krt183 2.39E−19 0.338485565 0.681 0.694 5.93E−15 PHX48 Krt18 Qsox11 1.75E−18 0.277977801 0.752 0.807 4.34E−14 PHX48 Qsox1 Tmsb4x1 2.19E−18 0.25903061 0.183 0.094 5.44E−14 PHX48 Tmsb4x Fdps1 1.22E−16 0.363303117 0.492 0.438 3.04E−12 PHX48 Fdps Oat4 1.69E−15 0.793230792 0.542 0.516 4.20E−11 PHX48 Oat Lect22 6.99E−15 0.388301276 0.427 0.352 1.74E−10 PHX48 Lect2 Apoc22 8.72E−15 0.290495283 0.803 0.837 2.17E−10 PHX48 Apoc2 Ssr41 1.66E−14 0.305225519 0.646 0.667 4.12E−10 PHX48 Ssr4 Cyp1a24 3.23E−12 0.325588327 0.708 0.707 8.03E−08 PHX48 Cyp1a2 Rpl13a 7.69E−10 0.263890271 0.766 0.831 1.91E−05 PHX48 Rpl13a Mlec 1.34E−07 0.324281741 0.436 0.417 0.003327101 PHX48 Mlec Pmvk 2.00E−07 0.254397796 0.359 0.322 0.004969378 PHX48 Pmvk Lss 7.67E−07 0.30143688 0.282 0.24 0.019046485 PHX48 Lss Sc4mol2 3.84E−06 0.255232899 0.584 0.62 0.095387919 PHX48 Sc4mol Smc4 4.95E−06 0.302249675 0.177 0.133 0.122794585 PHX48 Smc4 Tuba1c 1.47E−05 0.318082621 0.415 0.412 0.366264257 PHX48 Tuba1c Glul2 4.53E−05 0.369104744 0.203 0.277 1 PHX48 Glul Avpi1 0.000112837 0.313000373 0.409 0.416 1 PHX48 Avpi1 Rps24 0.001118688 0.252072758 0.574 0.64 1 PHX48 Rps24 Tubb5 0.004837713 0.325701472 0.304 0.294 1 PHX48 Tubb5 Sqle 0.007831353 0.262168232 0.379 0.392 1 PHX48 Sqle Tubb4b 0.009501966 0.323765623 0.347 0.352 1 PHX48 Tubb4b Lcn26 0 1.118815683 0.925 0.331 0 PHX120 Lcn2 Saa15 0 1.107521043 0.996 0.71 0 PHX120 Saa1 Saa25 0 1.008333835 0.948 0.457 0 PHX120 Saa2 Fgl14 0 0.874857754 0.993 0.864 0 PHX120 Fgl1 Saa44 0 0.858219404 0.982 0.799 0 PHX120 Saa4 Rnase43 0 0.818603379 0.993 0.926 0 PHX120 Rnase4 Orm26 0 0.807371375 0.813 0.225 0 PHX120 Orm2 Lrg13 0 0.788285793 0.982 0.844 0 PHX120 Lrg1 Itih33 0 0.775773488 0.991 0.933 0 PHX120 Itih3 Gm155644 0 0.753023538 1 0.973 0 PHX120 Gm15564 C4b1 0 0.738227617 0.98 0.898 0 PHX120 C4b C31 0 0.711130161 0.999 0.995 0 PHX120 C3 Lars24 0 0.709570617 1 0.997 0 PHX120 Lars2 Itih45 0 0.698397089 0.998 0.97 0 PHX120 Itih4 Cfh3 0 0.669226929 0.991 0.924 0 PHX120 Cfh Clu 0 0.594745205 0.997 0.968 0 PHX120 Clu Orm14 0 0.5647963 1 0.96 0 PHX120 Orm1 Hp4 0 0.561007835 0.999 0.999 0 PHX120 Hp Hpx4  1.09E−306 0.628252971 1 0.998  2.70E−302 PHX120 Hpx Plg  2.82E−295 0.468337901 0.997 0.973  7.01E−291 PHX120 Plg Ly6e2  1.18E−292 0.899345798 0.821 0.483  2.92E−288 PHX120 Ly6e Fga5  1.92E−290 0.521486803 0.999 0.997  4.76E−286 PHX120 Fga Kng1  1.96E−279 0.383479985 0.999 0.99  4.88E−275 PHX120 Kng1 Orm3  4.06E−270 0.509783113 0.47 0.115  1.01E−265 PHX120 Orm3 mmu-mir-62362  4.62E−269 0.989356763 0.989 0.884  1.15E−264 PHX120 mmu-mir-6236 Vtn3  1.71E−255 0.404732741 0.998 0.985  4.24E−251 PHX120 Vtn Prtn31  4.90E−246 0.298794716 0.271 0.034  1.22E−241 PHX120 Prtn3 Gm239351  5.60E−241 0.825787075 0.997 0.955  1.39E−236 PHX120 Gm23935 Fn1  5.04E−228 0.640566195 0.968 0.884  1.25E−223 PHX120 Fn1 Pzp  9.55E−224 0.425391077 0.999 0.988  2.37E−219 PHX120 Pzp Aldh1l1  1.54E−220 0.47413999 0.989 0.933  3.82E−216 PHX120 Aldh1l1 Tmem176b2  9.29E−219 0.590562164 0.901 0.693  2.31E−214 PHX120 Tmem176b Gm269245  1.34E−217 0.610417073 1 1  3.33E−213 PHX120 Gm26924 Lrp11  4.26E−214 0.735936027 0.874 0.671  1.06E−209 PHX120 Lrp1 Ambp1  4.27E−203 0.345542146 0.999 0.994  1.06E−198 PHX120 Ambp Hc1  1.93E−192 0.502827072 0.974 0.914  4.79E−188 PHX120 Hc Cp2  2.94E−183 0.408001782 0.995 0.961  7.30E−179 PHX120 Cp Qsox12  1.53E−176 0.50367789 0.93 0.783  3.80E−172 PHX120 Qsox1 Cyp2c704  2.83E−175 0.483246632 0.967 0.855  7.02E−171 PHX120 Cyp2c70 Lpl  2.92E−169 0.33278439 0.194 0.026  7.26E−165 PHX120 Lpl Hrg3  2.98E−169 0.439374294 0.966 0.864  7.41E−165 PHX120 Hrg Tmem176a2  9.05E−165 0.526399787 0.773 0.526  2.25E−160 PHX120 Tmem176a Mpeg11  1.84E−162 0.455546657 0.435 0.15  4.57E−158 PHX120 Mpeg1 Egfr4  2.19E−162 0.489699112 0.964 0.848  5.45E−158 PHX120 Egfr Prg41  8.97E−161 0.593630978 0.643 0.347  2.23E−156 PHX120 Prg4 Ifitm34  2.62E−158 0.454522399 0.944 0.828  6.51E−154 PHX120 Ifitm3 Cml22  5.40E−158 0.446681218 0.953 0.871  1.34E−153 PHX120 Cml2 Fgg5  5.05E−154 0.290840047 1 0.996  1.25E−149 PHX120 Fgg Cd5l2  4.20E−149 0.397997645 0.263 0.056  1.04E−144 PHX120 Cd5l Pck13  1.67E−147 0.360228951 0.999 0.976  4.14E−143 PHX120 Pck1 Serping12  2.59E−145 0.404994618 0.964 0.891  6.42E−141 PHX120 Serping1 Lbp  1.52E−141 0.532670555 0.702 0.445  3.78E−137 PHX120 Lbp Ang3  2.85E−139 0.532063038 0.874 0.703  7.08E−135 PHX120 Ang Serpina3n4  1.58E−136 0.356286933 0.948 0.743  3.92E−132 PHX120 Serpina3n Apcs4  7.41E−136 0.304899499 0.879 0.672  1.84E−131 PHX120 Apcs Comt3  1.12E−135 0.356782039 0.987 0.931  2.78E−131 PHX120 Comt Itih1  1.39E−120 0.385835499 0.936 0.855  3.45E−116 PHX120 Itih1 Ctsb1  4.89E−120 0.402671607 0.927 0.839  1.21E−115 PHX120 Ctsb Wfdc171  3.50E−119 0.26638224 0.195 0.038  8.70E−115 PHX120 Wfdc171 Lyz21  4.94E−118 0.337893409 0.222 0.049  1.23E−113 PHX120 Lyz2 Clec4f1  1.53E−117 0.360222876 0.282 0.078  3.79E−113 PHX120 Clec4f Serpina105  3.87E−114 0.378970318 0.896 0.746  9.61E−110 PHX120 Serpina10 H2-D11  4.89E−111 0.385804762 0.911 0.795  1.21E−106 PHX120 H2-D1 C4bp2  8.95E−110 0.354982898 0.934 0.842  2.22E−105 PHX120 C4bp Mug21  1.15E−102 0.431698452 0.881 0.773 2.85E−98 PHX120 Mug2 C1qb2 2.58E−95 0.255909874 0.208 0.053 6.41E−91 PHX120 C1qb Col18a11 4.56E−95 0.378250662 0.903 0.822 1.13E−90 PHX120 Col18a1 Fetub 8.03E−89 0.356300137 0.866 0.748 1.99E−84 PHX120 Fetub C8a2 2.98E−88 0.331149118 0.964 0.892 7.39E−84 PHX120 C8a n-R5-8s15 4.05E−87 0.323215543 0.578 0.308 1.00E−82 PHX120 n-R5-8s1 Apob2 7.41E−84 0.310671508 0.997 0.988 1.84E−79 PHX120 Apob Calr4 1.22E−83 0.273407417 0.961 0.903 3.04E−79 PHX120 Calr Slc22a7 5.17E−82 0.325996046 0.405 0.2 1.28E−77 PHX120 Slc22a7 Dap 8.86E−79 0.347190068 0.842 0.718 2.20E−74 PHX120 Dap Ldhd 2.25E−78 0.347265823 0.766 0.627 5.59E−74 PHX120 Ldhd Tat3 2.56E−78 0.300658052 0.988 0.934 6.35E−74 PHX120 Tat H6pd 1.14E−77 0.344480162 0.8 0.671 2.84E−73 PHX120 H6pd Abcb112 9.04E−77 0.346201855 0.877 0.809 2.24E−72 PHX120 Abcb11 Sephs24 4.17E−76 0.291789305 0.928 0.832 1.04E−71 PHX120 Sephs2 Cfi 2.06E−74 0.268077906 0.97 0.925 5.12E−70 PHX120 Cfi Tmsb4x2 1.69E−73 0.264490332 0.24 0.082 4.20E−69 PHX120 Tmsb4x Slc41a22 9.78E−72 0.296501328 0.446 0.235 2.43E−67 PHX120 Slc41a2 Scd13 4.74E−71 0.324102197 0.996 0.939 1.18E−66 PHX120 Scd1 Hamp21 8.82E−71 0.316130853 0.231 0.082 2.19E−66 PHX120 Hamp2 Serpinf2 2.11E−70 0.270856246 0.944 0.873 5.23E−66 PHX120 Serpinf2 Slc38a31 1.46E−69 0.280821059 0.936 0.874 3.64E−65 PHX120 Slc38a3 Bsg1 2.16E−67 0.284697866 0.892 0.81 5.36E−63 PHX120 Bsg Hspb83 1.11E−66 0.286758286 0.837 0.686 2.76E−62 PHX120 Hspb8 Myh94 4.39E−65 0.334214402 0.652 0.467 1.09E−60 PHX120 Myh9 Cpb21 5.07E−64 0.264151912 0.946 0.86 1.26E−59 PHX120 Cpb2 Kng2 1.50E−63 0.281257218 0.833 0.732 3.73E−59 PHX120 Kng2 Dhcr241 1.01E−62 0.289230487 0.92 0.854 2.52E−58 PHX120 Dhcr24 Pcx 3.13E−62 0.287981629 0.832 0.708 7.78E−58 PHX120 Pcx Lgals91 7.62E−60 0.293933007 0.912 0.814 1.89E−55 PHX120 Lgals9 Slc25a151 5.39E−57 0.261156509 0.896 0.795 1.34E−52 PHX120 Slc25a15 Plxnb2 5.25E−56 0.338890275 0.54 0.372 1.30E−51 PHX120 Plxnb2 Cpn21 2.28E−54 0.297606067 0.795 0.701 5.66E−50 PHX120 Cpn2 Gne1 3.58E−54 0.324486089 0.673 0.528 8.89E−50 PHX120 Gne Cyp3a13 3.22E−53 0.291486861 0.774 0.656 8.00E−49 PHX120 Cyp3a13 Habp2 1.40E−52 0.287786829 0.61 0.47 3.47E−48 PHX120 Habp2 F5 3.02E−50 0.30130754 0.84 0.773 7.49E−46 PHX120 F5 Apon 2.35E−48 0.264081329 0.811 0.703 5.84E−44 PHX120 Apon Rgn3 2.74E−48 0.311282552 0.911 0.8 6.81E−44 PHX120 Rgn Sardh1 7.55E−48 0.255777911 0.911 0.843 1.87E−43 PHX120 Sardh Hsph1 4.81E−47 0.316405276 0.512 0.351 1.19E−42 PHX120 Hsph1 Mbl22 1.07E−46 0.280531986 0.924 0.843 2.65E−42 PHX120 Mbl2 Abat1 3.38E−45 0.272187232 0.808 0.721 8.39E−41 PHX120 Abat Slc25a251 4.06E−45 0.275974133 0.866 0.767 1.01E−40 PHX120 Slc25a25 Kynu1 5.14E−45 0.266831158 0.728 0.623 1.28E−40 PHX120 Kynu Ugt1a1 3.78E−43 0.277601852 0.526 0.375 9.39E−39 PHX120 Ugt1a1 Stat33 6.51E−43 0.267640194 0.602 0.458 1.62E−38 PHX120 Stat3 Nbr11 1.83E−42 0.274748586 0.613 0.486 4.53E−38 PHX120 Nbr1 Xdh 2.51E−42 0.266596189 0.507 0.358 6.24E−38 PHX120 Xdh Cyp2e14 3.41E−42 0.442070005 0.88 0.811 8.46E−38 PHX120 Cyp2e1 Mafb1 1.11E−41 0.299984568 0.553 0.405 2.75E−37 PHX120 Mafb 1300002K09Rik 1.55E−41 0.274083731 0.673 0.562 3.85E−37 PHX120 1300002K09Rik Gulo1 2.72E−36 0.374663355 0.573 0.441 6.75E−32 PHX120 Gulo Uroc11 3.16E−36 0.267582019 0.782 0.689 7.85E−32 PHX120 Uroc1 Serpina6 1.33E−33 0.266334384 0.463 0.335 3.31E−29 PHX120 Serpina6 Ifi272 8.57E−28 0.275927448 0.565 0.45 2.13E−23 PHX120 Ifi27 Aldh1b1 2.35E−20 0.299248494 0.255 0.169 5.84E−16 PHX120 Aldh1b1 Mup197 0 2.345313651 1 0.764 0 UT Mup19 Mup176 0 2.220781802 1 0.873 0 UT Mup17 Mup66 0 2.187799459 0.992 0.682 0 UT Mup6 Mup97 0 2.1676942 0.976 0.446 0 UT Mup9 Mup186 0 2.052181205 0.997 0.653 0 UT Mup18 Mup57 0 1.497743401 0.839 0.437 0 UT Mup5 Mup119 0 1.449872866 1 0.91 0 UT Mup11 Ankrd555 0 1.403887011 0.696 0.35 0 UT Ankrd55 Mup43 0 1.400873792 0.898 0.468 0 UT Mup4 Mup156 0 1.2394731 0.617 0.171 0 UT Mup15 Gm137757 0 1.138463541 0.761 0.242 0 UT Gm13775 Mup166 0 1.034031769 0.934 0.638 0 UT Mup16 Mup215 0 0.969567043 0.929 0.617 0 UT Mup21 Mup86 0 0.774765659 0.373 0.093 0 UT Mup8 Mup34 0 0.731785979 1 1 0 UT Mup3 Mup126 0 0.633626671 0.86 0.598 0 UT Mup12 Gsta34 0 0.524565372 0.956 0.955 0 UT Gsta3 Cyb56 0 0.485470981 0.983 0.977 0 UT Cyb5 Akr1c62 0 0.477461748 0.971 0.946 0 UT Akr1c6 Mup203  7.83E−295 0.518904256 1 0.987  1.94E−290 UT Mup20 Car34  3.61E−292 0.48897551 0.974 0.929  8.96E−288 UT Car3 Acaa1b5  7.83E−288 0.432190174 0.969 0.86  1.94E−283 UT Acaa1b Mup135  5.10E−281 0.730853769 0.546 0.266  1.27E−276 UT Mup13 Fabp13  3.86E−269 0.324394469 1 0.995  9.59E−265 UT Fabp1 Selenbp25  1.39E−266 0.467273497 0.937 0.817  3.44E−262 UT Selenbp2 Elovl34  3.68E−264 0.539440847 0.827 0.632  9.14E−260 UT Elovl3 Apoa25  3.93E−247 0.254295816 1 0.999  9.76E−243 UT Apoa2 Serpina3c3  2.68E−243 0.508070161 0.385 0.133  6.66E−239 UT Serpina3c Sparcl1  4.86E−229 0.253616986 0.136 0  1.21E−224 UT Sparcl1 Cox4i14  1.79E−220 0.349876586 0.958 0.937  4.44E−216 UT Cox4i1 Cyp2b105  4.10E−218 0.833168678 0.542 0.299  1.02E−213 UT Cyp2b10 Ugt2b57  1.01E−213 0.319252422 0.959 0.937  2.51E−209 UT Ugt2b5 Uqcrq3  3.26E−208 0.390101345 0.951 0.919  8.10E−204 UT Uqcrq Hsd3b56  1.89E−182 0.552577049 0.587 0.371  4.70E−178 UT Hsd3b5 Gm4076  6.76E−179 0.310732462 0.184 0.028  1.68E−174 UT Gm4076 Rps141  1.79E−175 0.349394169 0.917 0.858  4.45E−171 UT Rsp14 2810007J24Rik2  1.71E−171 0.323006437 0.943 0.89  4.24E−167 UT 2810007J24Rik Mgst12  3.86E−170 0.266779567 0.997 0.994  9.59E−166 UT Mgst1 Igfbp22  2.57E−167 0.37970813 0.885 0.778  6.38E−163 UT Igfbp2 Cox6c4  5.12E−167 0.427825866 0.884 0.8  1.27E−162 UT Cox6c Mup24  2.49E−165 0.57964746 0.392 0.179  6.19E−161 UT Mup2 Cyp2c296  3.84E−165 0.413790763 0.93 0.78  9.53E−161 UT Cyp2c29 Serpina1a1  9.91E−159 0.27492561 0.991 0.971  2.46E−154 UT Serpina1a Serpina1e3  1.04E−150 0.256934164 0.999 0.993  2.59E−146 UT Serpina1e Inmt3  7.96E−146 0.419638578 0.884 0.855  1.98E−141 UT Inmt Cyp2a56  7.33E−145 0.571080729 0.555 0.334  1.82E−140 UT Cyp2a5 Hsd3b72  1.46E−143 0.388992153 0.798 0.715  3.63E−139 UT Hsd3b7 Mup76  6.63E−141 0.580202644 0.998 0.958  1.65E−136 UT Mup7 Cyp2c375  2.72E−138 0.393327144 0.608 0.371  6.74E−134 UT Cyp2c37 Rps2  8.56E−125 0.396723019 0.757 0.624  2.13E−120 UT Rps2 Ndufb112  1.77E−121 0.384829815 0.735 0.622  4.39E−117 UT Ndufb11 Cyp2d93  2.14E−119 0.251733819 0.959 0.934  5.33E−115 UT Cyp2d9 Prdx12  6.50E−118 0.275358573 0.927 0.903  1.61E−113 UT Prdx1 Cyp2c505  1.48E−117 0.366535791 0.888 0.76  3.67E−113 UT Cyp2c50 Oaz1  1.44E−112 0.371433095 0.75 0.664  3.58E−108 UT Oaz1 Cfhr21  9.38E−112 0.359716521 0.868 0.852  2.33E−107 UT Cfhr2 Tmem2052  4.61E−111 0.267844772 0.934 0.9  1.14E−106 UT Tmem205 Aadac3  2.52E−109 0.370440569 0.86 0.844  6.26E−105 UT Aadac Chchd22  5.87E−107 0.300651505 0.916 0.875  1.46E−102 UT Chchd2 Cox7b2  6.77E−107 0.338982432 0.878 0.816  1.68E−102 UT Cox7b Rps27l5  1.04E−102 0.30195065 0.849 0.759 2.57E−98 UT Rps27l Ndufa43 1.43E−99 0.304406354 0.889 0.846 3.55E−95 UT Ndufa4 Atp5f13 1.22E−98 0.297602439 0.869 0.847 3.03E−94 UT Atp5f1 C8g3 2.17E−97 0.25042614 0.91 0.881 5.39E−93 UT C8g Cyp2c545 7.72E−97 0.303236425 0.759 0.581 1.92E−92 UT Cyp2c54 Cyp8b16 2.00E−90 0.267497706 0.745 0.611 4.96E−86 UT Cyp8b1 Ugt2b12 4.18E−90 0.261161693 0.871 0.824 1.04E−85 UT Ugt2b1 Ndufb63 3.74E−89 0.3153639 0.759 0.675 9.30E−85 UT Ndufb6 Ahcy6 6.07E−84 0.250179307 0.916 0.847 1.51E−79 UT Ahcy Adck33 4.25E−81 0.29387974 0.764 0.708 1.06E−76 UT Adck3 Cyp1a25 3.41E−75 0.274168096 0.794 0.668 8.47E−71 UT Cyp1a2 Gm205944 1.13E−70 0.40164744 0.294 0.164 2.80E−66 UT Gm20594 Uqcrh2 1.78E−63 0.254384858 0.81 0.753 4.42E−59 UT Uqcrh Cml12 3.50E−63 0.26577242 0.757 0.717 8.69E−59 UT Cml1 Mup144 5.45E−63 0.506979284 0.616 0.509 1.35E−58 UT Mup14 Ndufa62 2.82E−61 0.261286559 0.798 0.751 7.01E−57 UT Ndufa6 Gm5096 1.47E−59 0.293645653 0.468 0.363 3.65E−55 UT Gm5096 Nudt75 2.05E−59 0.340585682 0.83 0.796 5.08E−55 UT Nudt7 Mup120 7.14E−58 0.561026142 0.583 0.483 1.77E−53 UT Mup1 Rnf1252 2.04E−57 0.264315058 0.493 0.382 5.07E−53 UT Rnf125 Fabp23 6.07E−56 0.283444626 0.622 0.522 1.51E−51 UT Fabp2 Prdx4 6.69E−54 0.288185238 0.607 0.541 1.66E−49 UT Prdx4 Rpl322 1.89E−51 0.263618639 0.757 0.692 4.68E−47 UT Rpl32 Cox7a22 1.53E−50 0.252198292 0.784 0.736 3.79E−46 UT Cox7a2 Ndufb41 3.21E−45 0.250792484 0.49 0.4 7.96E−41 UT Ndufb4 Ndufs61 1.46E−43 0.258085508 0.724 0.672 3.62E−39 UT Ndufs6 Gstp15 1.01E−42 0.281627196 0.822 0.759 2.50E−38 UT Gstp1 Ndufc21 1.23E−32 0.252253197 0.579 0.544 3.05E−28 UT Ndufc2 Ftl1 2.19E−24 0.319143693 0.409 0.358 5.43E−20 UT Ftl1 Zfp6832 2.64E−17 0.277346647 0.116 0.071 6.55E−13 UT Zfp683

TABLE 1b Treatment Markers Wilcox _val avg_logFC pct.1 pct.2 p_val_adj cluster gene Hbb-bs 0 2.5859 0.537 0.038 0 A6 Hbb-bs S100a9 0 1.34231 0.399 0.005 0 A6 S100a9 Hmox1 0 1.33957 0.558 0.026 0 A6 Hmox1 S100a8 0 1.12718 0.353 0.002 0 A6 S100a8 Tnfrsf12a  4.64E−274 1.10499 0.623 0.086  1.15E−269 A6 Tnfrsf12a Ccl6  8.63E−274 0.78681 0.274 0.006  2.14E−269 A6 Ccl6 Hilpda  3.58E−254 0.78035 0.403 0.028  8.90E−250 A6 Hilpda Mt2  4.30E−249 2.03768 0.938 0.405  1.07E−244 A6 Mt2 Srgn  3.95E−244 0.92893 0.284 0.01  9.80E−240 A6 Srgn Mt1  5.85E−244 2.32039 0.981 0.602  1.45E−239 A6 Mt1 Srxn1  1.13E−243 1.86421 0.821 0.239  2.80E−239 A6 Srxn1 Ppl  1.02E−233 0.86175 0.47 0.049  2.54E−229 A6 Ppl Slc16a6  7.70E−208 0.91397 0.47 0.058  1.91E−203 A6 Slc16a6 Gclc  1.87E−200 1.80238 0.962 0.764  4.64E−196 A6 Gclc Cdkn1a  1.22E−180 1.25188 0.702 0.195  3.04E−176 A6 Cdkn1a Plin2  1.48E−175 1.45429 0.943 0.742  3.67E−171 A6 Plin2 Tubb6  1.52E−170 0.57153 0.368 0.04  3.78E−166 A6 Tubb6 Actb  9.38E−169 1.0516 0.979 0.893  2.33E−164 A6 Actb Clec4f  3.46E−163 1.12406 0.339 0.034  8.59E−159 A6 Clec4f Chka  5.96E−156 1.40324 0.716 0.24  1.48E−151 A6 Chka Txnrd1  7.87E−143 1.37471 0.838 0.516  1.95E−138 A6 Txnrd1 Il1r1  5.63E−137 1.18867 0.683 0.247  1.40E−132 A6 Il1r1 Krt18  3.50E−128 1.22726 0.864 0.653  8.70E−124 A6 Krt18 Cidec  1.77E−123 0.30674 0.253 0.024  4.40E−119 A6 Cidec Krt8  8.28E−122 1.27348 0.826 0.564  2.06E−117 A6 Krt8 Klf6  8.56E−120 0.70668 0.382 0.066  2.13E−115 A6 Klf6 Ets2  2.20E−109 0.68055 0.415 0.087  5.47E−105 A6 Ets2 2010003K11Rik  3.63E−105 0.5729 0.396 0.081  9.02E−101 A6 2010003K11Rik Tmsb4x  6.61E−105 0.7911 0.332 0.055  1.64E−100 A6 Tmsb4x Cers6  1.33E−104 0.50708 0.332 0.055  3.29E−100 A6 Cers6 Plscr1  2.32E−103 0.4497 0.329 0.055 5.75E−99 A6 Plscr1 Rcan1 1.90E−94 0.70098 0.425 0.105 4.72E−90 A6 Rcan1 Gm26924 2.05E−93 0.72692 1 1 5.10E−89 A6 Gm26924 Myh9 2.39E−90 1.02483 0.718 0.401 5.92E−86 A6 Myh9 Fgg 1.41E−82 0.47508 0.986 0.995 3.50E−78 A6 Fgg Serpina3m 2.54E−82 0.79319 0.85 0.772 6.30E−78 A6 Serpina3m C230081A13Rik 5.32E−82 0.41842 0.279 0.049 1.32E−77 A6 C230081A13Rik Lrrc58 6.20E−82 0.93964 0.711 0.429 1.54E−77 A6 Lrrc58 Fga 8.43E−81 0.501 0.986 0.997 2.09E−76 A6 Fga Apoa4 3.02E−80 1.16604 0.721 0.434 7.51E−76 A6 Apoa4 Rell1 5.69E−79 0.57926 0.375 0.095 1.41E−74 A6 Rell1 Bcl2l1 9.17E−79 0.7415 0.501 0.182 2.28E−74 A6 Bcl2l1 Fgb 2.77E−76 0.47741 0.995 1 6.88E−72 A6 Fgb Lars2 4.16E−75 0.81426 1 0.995 1.03E−70 A6 Lars2 D10Wsu102e 3.45E−74 0.56983 0.37 0.097 8.56E−70 A6 D10Wsu102e Gsta1 2.23E−70 0.40892 0.32 0.073 5.53E−66 A6 Gsta1 Slc39a14 6.11E−70 0.91609 0.678 0.428 1.52E−65 A6 Slc39a14 Mrap 9.06E−70 0.86148 0.606 0.323 2.25E−65 A6 Mrap Gm15564 3.80E−66 0.78611 0.983 0.967 9.43E−62 A6 Gm15564 1700017B05Rik 1.21E−62 0.32766 0.255 0.052 3.00E−58 A6 1700017B05Rik Igfbp1 9.02E−61 1.0899 0.792 0.702 2.24E−56 A6 Igfbp1 Sdc4 7.44E−59 0.56725 0.909 0.892 1.85E−54 A6 Sdc4 Cldn14 1.21E−58 0.3695 0.32 0.085 3.00E−54 A6 Cldn14 Alb 4.24E−58 0.37487 1 1 1.05E−53 A6 Alb Sat1 3.50E−57 0.68873 0.47 0.193 8.68E−53 A6 Sat1 Hnf4a 7.04E−57 0.69625 0.835 0.805 1.75E−52 A6 Hnf4a Sqstm1 1.54E−56 0.69921 0.859 0.828 3.83E−52 A6 Sqstm1 Fam134b 3.22E−56 0.81523 0.678 0.482 8.00E−52 A6 Fam134b Nop58 2.76E−54 0.6343 0.492 0.216 6.86E−50 A6 Nop58 Efhd2 4.11E−53 0.57664 0.468 0.197 1.02E−48 A6 Efhd2 mmu-mir-6240 5.36E−53 1.03161 0.413 0.149 1.33E−48 A6 mmu-mir-6240 Trp53inp1 9.22E−52 0.88291 0.637 0.398 2.29E−47 A6 Trp53inp1 Epas1 5.89E−51 0.71377 0.604 0.373 1.46E−46 A6 Epas1 Apob 8.74E−50 0.48025 0.99 0.989 2.17E−45 A6 Apob Gcnt2 4.90E−49 0.50385 0.372 0.131 1.22E−44 A6 Gcnt2 Eif1a 5.09E−49 0.7228 0.599 0.373 1.26E−44 A6 Eif1a Insig2 1.13E−47 0.60809 0.854 0.83 2.80E−43 A6 Insig2 Serpina3n 2.16E−47 0.66415 0.747 0.658 5.38E−43 A6 Serpina3n Btg2 1.37E−46 0.76689 0.549 0.303 3.40E−42 A6 Btg2 Agpat9 3.40E−46 0.30485 0.277 0.077 8.45E−42 A6 Agpat9 Tra2a 1.23E−45 0.70805 0.337 0.114 3.05E−41 A6 Tra2a Creb3l2 1.45E−44 0.39712 0.329 0.11 3.61E−40 A6 Creb3l2 Stat3 1.26E−43 0.652 0.604 0.387 3.12E−39 A6 Stat3 Picalm 3.98E−43 0.67656 0.647 0.452 9.89E−39 A6 Picalm Tubb2a 8.70E−43 0.78599 0.618 0.443 2.16E−38 A6 Tubb2a Mat1a 9.42E−43 0.38887 0.986 0.973 2.34E−38 A6 Mat1a Malat1 3.57E−42 0.98537 0.871 0.75 8.87E−38 A6 Malat1 Cxadr 1.77E−41 0.65684 0.606 0.408 4.40E−37 A6 Cxadr Myo1e 5.97E−41 0.57864 0.475 0.237 1.48E−36 A6 Myo1e Bach1 8.93E−41 0.76858 0.461 0.236 2.22E−36 A6 Bach1 Eif5 1.03E−40 0.48089 0.816 0.786 2.56E−36 A6 Eif5 Tiparp 2.49E−40 0.52481 0.346 0.131 6.18E−36 A6 Tiparp Cltc 7.70E−40 0.68523 0.661 0.494 1.91E−35 A6 Cltc Ddx21 1.55E−39 0.65593 0.535 0.316 3.84E−35 A6 Ddx21 Mdn1 2.43E−39 0.30793 0.251 0.072 6.04E−35 A6 Mdn1 Heatr1 4.55E−39 0.38146 0.291 0.095 1.13E−34 A6 Heatr1 H3f3b 4.97E−39 0.71838 0.613 0.443 1.23E−34 A6 H3f3b Jmjd1c 3.17E−38 0.59632 0.47 0.239 7.87E−34 A6 Jmjd1c Dot1l 4.16E−38 0.38527 0.282 0.092 1.03E−33 A6 Dot1l Ctsl 6.53E−38 0.51275 0.878 0.88 1.62E−33 A6 Ctsl Slc10a2 1.11E−37 0.27045 0.255 0.077 2.75E−33 A6 Slc10a2 B4galt5 1.26E−37 0.42388 0.332 0.126 3.12E−33 A6 B4galt5 Rock2 2.45E−37 0.55518 0.425 0.199 6.08E−33 A6 Rock2 Dgkd 6.05E−37 0.35842 0.282 0.094 1.50E−32 A6 Dgkd Lcn2 1.67E−36 0.38757 0.301 0.106 4.14E−32 A6 Lcn2 Hspb8 1.95E−36 0.60892 0.709 0.633 4.84E−32 A6 Hspb8 Ugdh 3.59E−36 0.60855 0.721 0.647 8.92E−32 A6 Ugdh Ppan 9.70E−36 0.27669 0.255 0.079 2.41E−31 A6 Ppan Xbp1 1.86E−35 0.56939 0.692 0.611 4.62E−31 A6 Xbp1 Ddx5 2.16E−35 0.53966 0.685 0.543 5.37E−31 A6 Ddx5 Tnfrsf1a 2.76E−35 0.56814 0.508 0.305 6.86E−31 A6 Tnfrsf1a Tsr1 5.76E−35 0.33922 0.341 0.135 1.43E−30 A6 Tsr1 Itih3 6.08E−35 0.40422 0.907 0.913 1.51E−30 A6 Itih3 Ddx3x 6.10E−35 0.56117 0.692 0.592 1.51E−30 A6 Ddx3x St3gal1 9.22E−35 0.51699 0.473 0.262 2.29E−30 A6 St3gal1 Eaf1 1.20E−34 0.50717 0.427 0.212 2.98E−30 A6 Eaf1 Hsd17b13 2.16E−34 0.48038 0.864 0.761 5.37E−30 A6 Hsd17b13 Abca1 1.44E−33 0.65393 0.604 0.438 3.58E−29 A6 Abca1 Hif1a 4.80E−33 0.48757 0.427 0.213 1.19E−28 A6 Hif1a Tmem87b 1.08E−32 0.40541 0.351 0.151 2.68E−28 A6 Tmem87b Fkbp5 1.20E−32 0.45674 0.415 0.197 2.97E−28 A6 Fkbp5 C3 2.78E−32 0.27846 0.993 0.993 6.90E−28 A6 C3 Spred1 3.89E−31 0.35201 0.308 0.122 9.65E−27 A6 Spred1 Eef2 8.96E−31 0.40594 0.9 0.899 2.23E−26 A6 Eef2 Gnl3 1.03E−30 0.49018 0.501 0.3 2.56E−26 A6 Gnl3 Itih2 1.23E−30 0.39267 0.893 0.914 3.06E−26 A6 Itih2 Stk40 4.64E−30 0.493 0.382 0.184 1.15E−25 A6 Stk40 Tjp2 4.42E−29 0.39613 0.332 0.147 1.10E−24 A6 Tjp2 Lyst 1.82E−28 0.37173 0.31 0.127 4.52E−24 A6 Lyst Errfi1 2.21E−28 0.34209 0.943 0.931 5.50E−24 A6 Errfi1 Chic2 3.18E−28 0.3964 0.37 0.181 7.89E−24 A6 Chic2 Rad54l2 3.33E−28 0.36421 0.325 0.139 8.26E−24 A6 Rad54l2 Mfsd2a 4.59E−28 0.46105 0.465 0.263 1.14E−23 A6 Mfsd2a Sdad1 1.02E−27 0.29694 0.289 0.115 2.54E−23 A6 Sdad1 Bel3 2.52E−27 0.27406 0.277 0.109 6.26E−23 A6 Bel3 Neat1 3.08E−27 0.65541 0.31 0.135 7.66E−23 A6 Neat1 Asl 4.46E−27 0.41345 0.826 0.822 1.11E−22 A6 Asl Tcerg1 5.22E−27 0.34681 0.305 0.132 1.30E−22 A6 Tcerg1 Tacc2 5.92E−27 0.31276 0.289 0.116 1.47E−22 A6 Tacc2 Gpt2 9.88E−27 0.46947 0.764 0.767 2.45E−22 A6 Gpt2 Abhd2 2.12E−26 0.41489 0.37 0.181 5.25E−22 A6 Abhd2 Cyp4a14 2.69E−26 0.33337 0.776 0.554 6.69E−22 A6 Cyp4a14 Ptpn1 4.30E−26 0.38653 0.353 0.165 1.07E−21 A6 Ptpn1 Fndc3b 9.70E−26 0.34961 0.315 0.14 2.41E−21 A6 Fndc3b Tsku 3.63E−25 0.33318 0.327 0.148 9.01E−21 A6 Tsku Nolc1 6.52E−25 0.44449 0.363 0.183 1.62E−20 A6 Nolc1 Jak1 1.07E−24 0.54371 0.554 0.415 2.67E−20 A6 Jak1 Tsc22d2 2.31E−24 0.36291 0.353 0.175 5.73E−20 A6 Tsc22d2 Btg1 2.53E−24 0.39842 0.356 0.177 6.29E−20 A6 Btg1 Son 2.57E−24 0.4555 0.601 0.439 6.39E−20 A6 Son Lpin2 3.86E−24 0.51652 0.745 0.687 9.59E−20 A6 Lpin2 Iigp1 5.96E−24 0.64313 0.78 0.805 1.48E−19 A6 Iigp1 St3gal5 6.19E−24 0.43579 0.706 0.581 1.54E−19 A6 St3gal5 n-R5-8s1 1.02E−23 0.40051 0.308 0.135 2.53E−19 A6 n-R5-8s1 Eif4g2 1.15E−23 0.41256 0.757 0.748 2.86E−19 A6 Eif4g2 Gjb2 2.31E−23 0.50382 0.678 0.644 5.73E−19 A6 Gjb2 Dusp16 1.08E−22 0.42732 0.372 0.203 2.68E−18 A6 Dusp16 Pfkfb2 1.30E−22 0.26939 0.26 0.108 3.23E−18 A6 Pfkfb2 Tars 1.56E−22 0.47178 0.666 0.587 3.87E−18 A6 Tars Rora 2.50E−22 0.54096 0.549 0.433 6.22E−18 A6 Rora Plec 3.98E−22 0.41883 0.422 0.244 9.88E−18 A6 Plec Gm26917 6.93E−22 0.42391 0.382 0.204 1.72E−17 A6 Gm26917 Mpeg1 1.75E−21 0.46679 0.263 0.113 4.34E−17 A6 Mpeg1 Mat2a 3.17E−21 0.47583 0.487 0.332 7.86E−17 A6 Mat2a Gtpbp4 3.37E−21 0.46234 0.477 0.317 8.37E−17 A6 Gtpbp4 Ranbp2 4.52E−21 0.50743 0.566 0.435 1.12E−16 A6 Ranbp2 Map2k3 6.02E−21 0.41497 0.427 0.262 1.50E−16 A6 Map2k3 Mcl1 6.44E−21 0.5249 0.573 0.434 1.60E−16 A6 Mcl1 Slc20a1 1.39E−20 0.32604 0.284 0.131 3.44E−16 A6 Slc20a1 Cars 1.86E−20 0.30674 0.329 0.166 4.61E−16 A6 Cars Ywhag 3.03E−20 0.51318 0.518 0.392 7.52E−16 A6 Ywhag Retsat 4.73E−20 0.29183 0.845 0.85 1.18E−15 A6 Retsat Etf1 4.99E−20 0.45256 0.606 0.499 1.24E−15 A6 Etf1 Epb4.1 6.09E−20 0.46777 0.537 0.403 1.51E−15 A6 Epb4.1 Myl12a 8.41E−20 0.40288 0.461 0.306 2.09E−15 A6 Myl12a Dusp6 3.85E−19 0.50868 0.482 0.335 9.57E−15 A6 Dusp6 Gm20594 7.21E−19 0.4405 0.442 0.259 1.79E−14 A6 Gm20594 Lrg1 7.52E−19 0.3324 0.783 0.797 1.87E−14 A6 Lrg1 Dkc1 8.07E−19 0.30545 0.315 0.162 2.00E−14 A6 Dkc1 App 1.30E−18 0.33806 0.315 0.162 3.23E−14 A6 App Rnd3 1.41E−18 0.32675 0.284 0.14 3.50E−14 A6 Rnd3 Ncl 1.56E−18 0.38819 0.69 0.639 3.88E−14 A6 Ncl Tatdn2 1.76E−18 0.32476 0.334 0.176 4.36E−14 A6 Tatdn2 Fam107b 2.12E−18 0.41622 0.449 0.307 5.26E−14 A6 Fam107b Tns1 3.23E−18 0.40012 0.403 0.254 8.02E−14 A6 Tns1 Phc2 3.78E−18 0.29899 0.284 0.141 9.39E−14 A6 Phc2 Tbc1d15 3.97E−18 0.43222 0.461 0.319 9.86E−14 A6 Tbc1d15 Dst 3.98E−18 0.44734 0.43 0.276 9.87E−14 A6 Dst Lmo4 4.29E−18 0.29625 0.308 0.162 1.06E−13 A6 Lmo4 Egr1 5.65E−18 0.53704 0.589 0.481 1.40E−13 A6 Egr1 Hnrnpdl 8.07E−18 0.39933 0.406 0.254 2.00E−13 A6 Hnrnpdl Aff4 1.70E−17 0.53634 0.537 0.423 4.23E−13 A6 Aff4 Gnl2 1.83E−17 0.35803 0.384 0.235 4.55E−13 A6 Gnl2 Lrrfip1 2.21E−17 0.41083 0.37 0.221 5.49E−13 A6 Lrrfip1 Aass 2.35E−17 0.40708 0.747 0.763 5.83E−13 A6 Aass Kif5b 8.07E−17 0.45223 0.494 0.379 2.00E−12 A6 Kif5b Wbp1l 1.01E−16 0.3897 0.697 0.683 2.52E−12 A6 Wbp1l Stom 1.12E−16 0.29996 0.329 0.184 2.77E−12 A6 Stom Arhgef12 1.63E−16 0.48561 0.578 0.494 4.05E−12 A6 Arhgef12 Pxk 4.69E−16 0.26523 0.303 0.161 1.16E−11 A6 Pxk Prrc2c 6.21E−16 0.39059 0.415 0.266 1.54E−11 A6 Prrc2c Sds 6.91E−16 0.35155 0.73 0.632 1.72E−11 A6 Sds Mybbp1a 7.16E−16 0.4018 0.396 0.263 1.78E−11 A6 Mybbp1a Wdr43 8.36E−16 0.30829 0.353 0.208 2.08E−11 A6 Wdr43 Mmp14 9.37E−16 0.25714 0.253 0.125 2.33E−11 A6 Mmp14 Ptpn2 9.68E−16 0.27096 0.255 0.124 2.40E−11 A6 Ptpn2 Mak16 1.01E−15 0.28973 0.267 0.134 2.51E−11 A6 Mak16 Plk3 1.73E−15 0.41583 0.413 0.269 4.29E−11 A6 Plk3 Tm4sf4 2.46E−15 0.40056 0.484 0.363 6.11E−11 A6 Tm4sf4 Cyp39a1 4.02E−15 0.29958 0.305 0.171 9.99E−11 A6 Cyp39a1 Nedd4l 4.88E−15 0.26354 0.332 0.189 1.21E−10 A6 Nedd4l Ptpn12 6.24E−15 0.30933 0.263 0.135 1.55E−10 A6 Ptpn12 Map3k5 6.60E−15 0.31306 0.346 0.206 1.64E−10 A6 Map3k5 Nars 7.95E−15 0.36869 0.606 0.539 1.97E−10 A6 Nars Ptp4a1 9.30E−15 0.25171 0.334 0.192 2.31E−10 A6 Ptp4a1 Gm24245 1.17E−14 0.49843 0.422 0.269 2.89E−10 A6 Gm24245 Ifrd1 1.21E−14 0.47648 0.365 0.226 3.00E−10 A6 Ifrd1 AA474408 1.38E−14 0.26642 0.274 0.142 3.42E−10 A6 AA474408 Zyx 2.09E−14 0.27986 0.263 0.137 5.20E−10 A6 Zyx Smg1 2.32E−14 0.30447 0.265 0.141 5.76E−10 A6 Smg1 Man2a1 3.27E−14 0.34393 0.671 0.659 8.13E−10 A6 Man2a1 Lrrfip2 3.29E−14 0.35649 0.384 0.247 8.16E−10 A6 Lrrfip2 Ppp1r12a 3.38E−14 0.32516 0.317 0.182 8.39E−10 A6 Ppp1r12a Chd1 4.71E−14 0.31413 0.377 0.243 1.17E−09 A6 Chd1 Lpgat1 5.37E−14 0.4435 0.618 0.593 1.33E−09 A6 Lpgat1 Palld 6.63E−14 0.30837 0.353 0.218 1.65E−09 A6 Palld H2-D1 6.78E−14 0.29863 0.766 0.781 1.68E−09 A6 H2-D1 Grn 7.22E−14 0.37381 0.582 0.499 1.79E−09 A6 Grn Fus 1.11E−13 0.33882 0.394 0.267 2.76E−09 A6 Fus Litaf 1.26E−13 0.35117 0.451 0.34 3.13E−09 A6 Litaf Mki67ip 1.50E−13 0.31217 0.344 0.212 3.73E−09 A6 Mki67ip Lcp1 2.39E−13 0.4649 0.492 0.365 5.94E−09 A6 Lcp1 mt-Rnr1 2.60E−13 0.39009 1 1 6.45E−09 A6 mt-Rnr1 Ctsb 2.79E−13 0.46911 0.804 0.82 6.94E−09 A6 Ctsb Sptbn1 3.21E−13 0.37622 0.439 0.325 7.98E−09 A6 Sptbn1 Sfpq 5.31E−13 0.34485 0.406 0.277 1.32E−08 A6 sfpq Tgm2 5.71E−13 0.36214 0.446 0.314 1.42E−08 A6 Tgm2 Eif4g1 1.45E−12 0.31441 0.723 0.719 3.60E−08 A6 Eif4g1 Fn1 2.32E−12 0.2852 0.847 0.866 5.76E−08 A6 Fn1 Purb 2.57E−12 0.31082 0.341 0.219 6.37E−08 A6 Purb Phlda1 2.84E−12 0.47234 0.494 0.429 7.05E−08 A6 Phlda1 Atp2a2 3.95E−12 0.36462 0.616 0.575 9.81E−08 A6 Atp2a2 Etnppl 6.99E−12 0.30441 0.706 0.62 1.74E−07 A6 Etnppl Akap13 7.44E−12 0.44359 0.406 0.282 1.85E−07 A6 Akap13 Wdr26 1.07E−11 0.37235 0.549 0.472 2.66E−07 A6 Wdr26 Huwe1 1.08E−11 0.33358 0.492 0.38 2.69E−07 A6 Huwe1 Cald1 1.16E−11 0.29347 0.766 0.795 2.89E−07 A6 Cald1 Ankrd11 1.30E−11 0.37149 0.389 0.263 3.24E−07 A6 Ankrd11 Mbnl1 2.38E−11 0.34827 0.492 0.394 5.91E−07 A6 Mbnl1 Mug2 2.45E−11 0.2773 0.776 0.77 6.09E−07 A6 Mug2 Rn7sk 2.61E−11 0.2776 0.339 0.212 6.48E−07 A6 Rn7sk Anxa5 2.84E−11 0.35799 0.391 0.278 7.05E−07 A6 Anxa5 Metap2 4.08E−11 0.32796 0.453 0.353 1.01E−06 A6 Metap2 Shb 4.85E−11 0.28309 0.382 0.264 1.20E−06 A6 Shb Gsr 4.90E−11 0.39239 0.453 0.346 1.22E−06 A6 Gsr Gsk3b 5.45E−11 0.35405 0.384 0.272 1.35E−06 A6 Gsk3b Kdelr2 5.86E−11 0.36902 0.484 0.413 1.45E−06 A6 Kdelr2 Tjp1 1.36E−10 0.2529 0.251 0.142 3.37E−06 A6 Tjp1 Sf1 2.46E−10 0.27771 0.351 0.233 6.11E−06 A6 Sf1 Dhx9 3.77E−10 0.30561 0.427 0.319 9.37E−06 A6 Dhx9 Smap2 4.08E−10 0.31706 0.363 0.246 1.01E−05 A6 Smap2 Chmp4b 4.61E−10 0.29391 0.442 0.344 1.14E−05 A6 Chmp4b Cxcl1 5.14E−10 0.3092 0.444 0.334 1.28E−05 A6 Cxcl1 Snx10 5.28E−10 0.26407 0.341 0.232 1.31E−05 A6 Snx10 Pacsin2 5.77E−10 0.34257 0.37 0.264 1.43E−05 A6 Pacsin2 Cast 7.34E−10 0.34192 0.399 0.293 1.82E−05 A6 Cast Akap11 7.52E−10 0.29723 0.351 0.24 1.87E−05 A6 Akap11 Srsf11 7.58E−10 0.35423 0.418 0.313 1.88E−05 A6 Srsf11 Reep3 9.04E−10 0.33507 0.535 0.502 2.24E−05 A6 Reep3 mmu-mir-6236 1.28E−09 0.42047 0.831 0.853 3.19E−05 A6 mmu-mir-6236 Atf4 2.02E−09 0.28671 0.58 0.505 5.02E−05 A6 Atf4 Clic4 2.32E−09 0.2811 0.368 0.265 5.77E−05 A6 Clic4 Ubr4 2.43E−09 0.29161 0.411 0.302 6.03E−05 A6 Ubr4 Por 2.58E−09 0.26872 0.704 0.721 6.42E−05 A6 Por Bptf 2.63E−09 0.28182 0.332 0.222 6.53E−05 A6 Bptf Zbtb20 2.91E−09 0.37805 0.566 0.519 7.23E−05 A6 Zbtb20 Dync1h1 3.26E−09 0.34196 0.379 0.275 8.10E−05 A6 Dync1h1 Rlim 3.27E−09 0.27576 0.305 0.199 8.12E−05 A6 Rlim Birc6 4.85E−09 0.2922 0.446 0.34 0.0001204 A6 Birc6 Atp1b1 5.41E−09 0.31397 0.391 0.294 0.0001342 A6 Atp1b1 Slc25a47 6.75E−09 0.28843 0.869 0.931 0.0001677 A6 Slc25a47 Slc25a51 7.23E−09 0.25329 0.308 0.203 0.0001795 A6 Slc25a51 Jhdm1d 7.29E−09 0.25415 0.279 0.177 0.0001811 A6 Jhdm1d Steap4 9.00E−09 0.3653 0.37 0.275 0.0002235 A6 Steap4 Mapkapk2 9.71E−09 0.3053 0.396 0.294 0.0002411 A6 Mapkapk2 Gtf2a2 1.09E−08 0.2654 0.379 0.28 0.0002716 A6 Gtf2a2 Slc4a4 1.12E−08 0.29527 0.513 0.439 0.0002785 A6 Slc4a4 Tbl1xr1 1.79E−08 0.25532 0.341 0.246 0.0004436 A6 Tbl1xr1 Sbno1 1.89E−08 0.29621 0.394 0.301 0.0004698 A6 Sbno1 Nrp1 1.98E−08 0.32032 0.391 0.295 0.0004928 A6 Nrp1 Tpr 2.01E−08 0.35244 0.501 0.429 0.0004993 A6 Tpr Kif21a 2.01E−08 0.33336 0.461 0.377 0.0005003 A6 Kif21a Mdm2 2.06E−08 0.27581 0.305 0.204 0.0005108 A6 Mdm2 Ddx6 2.13E−08 0.34733 0.527 0.46 0.0005298 A6 Ddx6 Rbm25 2.41E−08 0.36502 0.461 0.369 0.0005983 A6 Rbm25 Uhrf1bp1l 2.44E−08 0.31928 0.399 0.306 0.0006069 A6 Uhrf1bp1l Cep85 3.36E−08 0.27083 0.313 0.215 0.0008335 A6 Cep85 Hmgcr 3.52E−08 0.3449 0.425 0.343 0.0008739 A6 Hmgcr Saa2 4.22E−08 0.38921 0.315 0.221 0.0010472 A6 Saa2 Tnks2 5.05E−08 0.26738 0.358 0.265 0.0012544 A6 Tnks2 Net1 5.81E−08 0.32011 0.408 0.324 0.0014419 A6 Net1 Rangap1 6.81E−08 0.27147 0.387 0.298 0.0016908 A6 Rangap1 Atp13a3 8.04E−08 0.29804 0.532 0.494 0.0019974 A6 Atp13a3 Tmed5 9.87E−08 0.26284 0.594 0.587 0.0024518 A6 Tmed5 Atp2b1 1.14E−07 0.28938 0.334 0.239 0.0028301 A6 Atp2b1 Ell2 1.24E−07 0.3073 0.535 0.508 0.0030817 A6 Ell2 Eif4a1 1.50E−07 0.26079 0.418 0.331 0.0037153 A6 Eif4a1 Macf1 1.58E−07 0.34781 0.377 0.287 0.0039148 A6 Macf1 Srrm2 1.83E−07 0.28659 0.456 0.372 0.0045319 A6 Srrm2 Brd2 1.86E−07 0.45982 0.542 0.493 0.0046088 A6 Brd2 Ipo7 1.95E−07 0.26719 0.334 0.241 0.0048465 A6 Ipo7 Cap1 2.19E−07 0.28532 0.356 0.261 0.0054372 A6 Cap1 Lrrc59 2.71E−07 0.30238 0.422 0.354 0.00672 A6 Lrrc59 Scaf11 3.09E−07 0.28756 0.449 0.382 0.0076803 A6 Scaf11 Phf20l1 3.47E−07 0.26568 0.372 0.282 0.0086272 A6 Phf20l1 Hipk3 3.52E−07 0.26049 0.396 0.309 0.0087524 A6 Hipk3 Prpf19 3.65E−07 0.25658 0.432 0.356 0.0090721 A6 Prpf19 Actr3 4.09E−07 0.26383 0.36 0.273 0.0101555 A6 Actr3 Gfra1 5.26E−07 0.27582 0.599 0.583 0.0130598 A6 Gfra1 Dnajc5 5.58E−07 0.26355 0.372 0.294 0.0138673 A6 Dnajc5 Gm5424 7.53E−07 0.2647 0.411 0.325 0.0186934 A6 Gm5424 Ppip5k2 7.82E−07 0.30024 0.344 0.254 0.0194128 A6 Ppip5k2 Yap1 8.00E−07 0.26153 0.375 0.288 0.019873 A6 Yap1 mt-Co1 1.20E−06 0.35102 0.998 0.988 0.0297443 A6 mt-Co1 Mgea5 1.25E−06 0.29042 0.413 0.333 0.0310796 A6 Mgea5 Kpna1 1.55E−06 0.25545 0.363 0.286 0.0384703 A6 Kpna1 Atf6 1.79E−06 0.29222 0.432 0.365 0.0444322 A6 Atf6 Ivns1abp 1.94E−06 0.27551 0.446 0.398 0.0482394 A6 Ivns1abp Dnaja2 2.46E−06 0.29931 0.516 0.482 0.0612092 A6 Dnaja2 Ctsc 2.59E−06 0.25762 0.403 0.321 0.064323 A6 Ctsc Kdm5a 2.84E−06 0.31018 0.308 0.221 0.0705376 A6 Kdm5a Abce1 2.87E−06 0.25023 0.437 0.365 0.0712986 A6 Abce1 Rsl1d1 3.31E−06 0.27488 0.47 0.423 0.0820794 A6 Rsl1d1 Eprs 4.18E−06 0.29766 0.566 0.558 0.1038218 A6 Eprs Hnrnpu 5.29E−06 0.25058 0.625 0.651 0.1313752 A6 Hnrnpu H6pd 5.50E−06 0.25615 0.623 0.652 0.1366428 A6 H6pd mt-Nd5 6.52E−06 0.34113 0.983 0.969 0.1619437 A6 mt-Nd5 Rnf169 7.00E−06 0.29632 0.315 0.235 0.1737208 A6 Rnf169 Rap1b 7.33E−06 0.28412 0.406 0.335 0.1819444 A6 Rap1b Chuk 8.66E−06 0.29548 0.523 0.495 0.2149235 A6 Chuk Sf3b1 9.81E−06 0.25061 0.508 0.475 0.2435822 A6 Sf3b1 Serinc3 1.22E−05 0.28119 0.525 0.498 0.3039179 A6 Serinc3 Pi4k2a 1.25E−05 0.32702 0.425 0.381 0.3103073 A6 Pi4k2a Alcam 1.35E−05 0.26477 0.396 0.329 0.334205 A6 Alcam Gadd45a 1.39E−05 0.28209 0.251 0.178 0.3447616 A6 Gadd45a Diap1 1.79E−05 0.28157 0.382 0.306 0.4448124 A6 Diap1 Ddx3y 3.35E−05 0.27782 0.47 0.43 0.8318918 A6 Ddx3y Eif4b 3.52E−05 0.27888 0.542 0.521 0.8734269 A6 Eif4b Nploc4 5.58E−05 0.25153 0.351 0.28 1 A6 Nploc4 Nucks1 7.26E−05 0.26038 0.532 0.517 1 A6 Nucks1 Tab2 7.82E−05 0.29307 0.425 0.374 1 A6 Tab2 Slc35d1 8.85E−05 0.25379 0.489 0.496 1 A6 Slc35d1 Abcc2 8.98E−05 0.26003 0.632 0.654 1 A6 Abcc2 Atp1a1 9.45E−05 0.29131 0.53 0.538 1 A6 Atp1a1 Slc40a1 0.00029608 0.34995 0.456 0.417 1 A6 Slc40a1 Zfp106 0.00031964 0.27067 0.391 0.333 1 A6 Zfp106 Ier2 0.00036702 0.25075 0.551 0.517 1 A6 Ier2 Trip11 0.00058924 0.28702 0.341 0.284 1 A6 Trip11 Srsf5 0.00064161 0.25349 0.387 0.34 1 A6 Srsf5 Spag9 0.00172919 0.25323 0.415 0.373 1 A6 Spag9 Tln1 0.00250885 0.2937 0.31 0.259 1 A6 Tln1 Riok3 0.0030185 0.25892 0.43 0.406 1 A6 Riok3 mt-Nd6 0.00348624 0.29062 0.527 0.502 1 A6 mt-Nd6 Gm269241 0 1.25316 1 1 0 A24 Gm26924 n-R5-8s11 0 1.15081 0.522 0.075 0 A24 n-R5-8s1 Grip2 0 0.87737 0.475 0.003 0 A24 Grip2 Fga1 0 0.76204 0.998 0.996 0 A24 Fga Fgb1 0 0.68103 1 0.999 0 A24 Fgb Fgg1 0 0.6334 0.999 0.993 0 A24 Fgg Lars21  1.08E−286 1.49313 0.998 0.995  2.69E−282 A24 Lars2 Sephs21  1.58E−286 0.85357 0.949 0.785  3.91E−282 A24 Sephs2 Fgl1  5.87E−275 0.87406 0.938 0.799  1.46E−270 A24 Fgl1 Gm24601  4.02E−274 0.93244 0.404 0.047  9.99E−270 A24 Gm24601 Gm155641  3.89E−272 1.55543 0.982 0.965  9.67E−268 A24 Gm15564 Calr1  5.92E−193 0.61158 0.952 0.882  1.47E−188 A24 Calr Pdia31  3.00E−171 0.64241 0.895 0.805  7.45E−167 A24 Pdia3 Hyou1  1.92E−169 0.84359 0.717 0.423  4.77E−165 A24 Hyou1 Saa21  1.56E−157 1.0091 0.52 0.172  3.88E−153 A24 Saa2 Hsp90b11  2.63E−155 0.54513 0.954 0.948  6.53E−151 A24 Hsp90b1 Sepp1  5.04E−153 0.32603 1 1  1.25E−148 A24 Sepp1 Hspa5  1.66E−152 0.48995 0.974 0.954  4.12E−148 A24 Hspa5 Orm1  6.97E−135 0.46612 0.963 0.942  1.73E−130 A24 Orm1 Itih4  2.79E−129 0.4689 0.974 0.956  6.93E−125 A24 Itih4 Egfr  2.69E−128 0.62342 0.882 0.802  6.67E−124 A24 Egfr Glud1  1.70E−115 0.42115 0.958 0.921  4.22E−111 A24 Glud1 HP  2.71E−113 0.36435 0.998 0.999  6.73E−109 A24 HP Mup71  1.68E−111 0.26813 0.985 0.965  4.16E−107 A24 Mup7 Serpina101  2.00E−108 0.57073 0.813 0.667  4.97E−104 A24 Serpina10 Rnase41  2.35E−108 0.55401 0.963 0.898  5.83E−104 A24 Rnase4 Scd11  2.78E−104 0.55857 0.98 0.925  6.90E−100 A24 Scd1 Eef1a1  2.17E−101 0.45614 0.919 0.858 5.38E−97 A24 Eef1a1 Saa1  2.48E−100 0.78117 0.792 0.549 6.16E−96 A24 Saa1 C8b1 1.53E−99 0.44014 0.898 0.871 3.79E−95 A24 C8b Hdlbp 2.71E−98 0.52785 0.853 0.753 6.72E−94 A24 Hdlbp Cyp2c701 7.78E−90 0.47953 0.89 0.823 1.93E−85 A24 Cyp2c70 P4hb1 2.74E−89 0.33254 0.973 0.945 6.82E−85 A24 P4hb Apcs 5.47E−89 0.60591 0.738 0.556 1.36E−84 A24 Apcs Creld2 5.15E−88 0.59406 0.583 0.352 1.28E−83 A24 Creld2 C91 2.56E−84 0.37576 0.952 0.926 6.35E−80 A24 C9 Orm2 5.62E−84 0.30465 0.285 0.081 1.40E−79 A24 Orm2 Ssr3 1.77E−83 0.48612 0.765 0.642 4.40E−79 A24 Ssr3 Pzp 4.35E−83 0.35431 0.984 0.988 1.08E−78 A24 Pzp C31 2.09E−82 0.32381 0.996 0.993 5.18E−78 A24 C3 Arrdc31 1.19E−81 0.49892 0.52 0.272 2.97E−77 A24 Arrdc3 Saa41 1.26E−81 0.47628 0.823 0.734 3.13E−77 A24 Saa4 Fn11 3.93E−80 0.55363 0.905 0.858 9.76E−76 A24 Fn1 Cfh 3.78E−79 0.45472 0.921 0.904 9.38E−75 A24 Cfh Cat 3.96E−78 0.28564 0.978 0.977 9.84E−74 A24 Cat Actb1 4.53E−78 0.32283 0.919 0.895 1.12E−73 A24 Actb Pdia41 2.83E−76 0.52087 0.733 0.616 7.02E−72 A24 Pdia4 Sc5d1 4.88E−76 0.39881 0.879 0.797 1.21E−71 A24 Sc5d Steap41 5.67E−76 0.46634 0.481 0.243 1.41E−71 A24 Steap4 C8a 1.03E−72 0.424 0.902 0.877 2.55E−68 A24 C8a Pgrmc1 1.30E−70 0.30757 0.953 0.947 3.22E−66 A24 Pgrmc1 Itih31 3.45E−70 0.39323 0.931 0.909 8.58E−66 A24 Itih3 Nudt71 3.41E−69 0.34726 0.884 0.74 8.47E−65 A24 Nudt7 Hc 5.21E−67 0.38899 0.905 0.904 1.29E−62 A24 Hc Tram1 1.87E−66 0.42942 0.7 0.545 4.63E−62 A24 Tram1 Myh91 1.24E−65 0.49194 0.595 0.388 3.08E−61 A24 Myh9 Mup121 1.65E−65 0.45328 0.799 0.759 4.10E−61 A24 Mup12 Gm269171 8.37E−65 0.78706 0.391 0.183 2.08E−60 A24 Gm26917 Dnajc3 2.12E−64 0.38899 0.85 0.808 5.26E−60 A24 Dnajc3 Hao1 7.24E−61 0.39162 0.83 0.767 1.80E−56 A24 Hao1 Pdia61 8.25E−60 0.42093 0.779 0.702 2.05E−55 A24 Pdia6 Apob1 9.57E−60 0.35398 0.983 0.99 2.38E−55 A24 Apob Manf 2.64E−58 0.46525 0.632 0.478 6.55E−54 A24 Manf Pdcd41 4.76E−58 0.46791 0.677 0.542 1.18E−53 A24 Pdcd4 AI1823711 9.61E−58 0.42306 0.747 0.654 2.39E−53 A24 AI182371 Comt1 5.49E−57 0.30202 0.928 0.92 1.36E−52 A24 Comt Cpb21 2.17E−56 0.33155 0.879 0.827 5.40E−52 A24 Cpb2 Serp1 2.18E−55 0.40205 0.809 0.725 5.42E−51 A24 Serp1 Cml21 5.80E−55 0.34556 0.896 0.849 1.44E−50 A24 Cml2 Elovl2 1.73E−53 0.38067 0.826 0.751 4.29E−49 A24 Elovl2 mmu-mir-62361 6.37E−53 0.84589 0.896 0.843 1.58E−48 A24 mmu-mir-6236 Iigp11 1.35E−52 0.33355 0.832 0.798 3.36E−48 A24 Iigp1 Calm1 1.03E−50 0.37016 0.794 0.759 2.56E−46 A24 Calm1 Cps1 2.48E−50 0.27751 0.982 0.977 6.16E−46 A24 Cps1 Eif4g21 6.14E−50 0.35147 0.8 0.739 1.52E−45 A24 Eif4g2 Acox1 1.63E−48 0.27431 0.966 0.968 4.05E−44 A24 Acox1 Fndc3b1 3.80E−48 0.32024 0.291 0.125 9.44E−44 A24 Fndc3b Slc41a2 1.01E−47 0.28796 0.302 0.132 2.51E−43 A24 Slc41a2 Nr1d2 5.02E−47 0.38547 0.442 0.263 1.25E−42 A24 Nr1d2 Insig1 1.30E−46 0.41247 0.626 0.487 3.23E−42 A24 Insig1 Aox31 1.16E−45 0.34889 0.916 0.896 2.88E−41 A24 Aox3 Spcs3 6.70E−45 0.39071 0.483 0.325 1.66E−40 A24 Spcs3 Atxn1 2.39E−44 0.32504 0.311 0.148 5.93E−40 A24 Atxn1 Cmah 3.14E−44 0.42429 0.607 0.472 7.80E−40 A24 Cmah Pnpla7 4.00E−44 0.39659 0.678 0.561 9.93E−40 A24 Pnpla7 Dnajc12 1.33E−42 0.32405 0.275 0.125 3.31E−38 A24 Dnajc12 Atp8b1 3.45E−42 0.36101 0.391 0.221 8.56E−38 A24 Atp8b1 Hspa13 3.59E−42 0.34197 0.404 0.237 8.92E−38 A24 Hspa13 AA4744081 1.41E−41 0.41482 0.278 0.126 3.51E−37 A24 AA474408 Canx 1.09E−40 0.27706 0.872 0.862 2.70E−36 A24 Canx Tmed7 1.35E−40 0.3715 0.563 0.417 3.35E−36 A24 Tmed7 Il13ra1 1.42E−40 0.28891 0.33 0.168 3.53E−36 A24 Il13ra1 Sdf2l1 2.54E−40 0.30777 0.412 0.24 6.31E−36 A24 Sdf2l1 Acly 5.13E−40 0.41013 0.597 0.448 1.27E−35 A24 Acly Cxcl11 8.60E−40 0.45301 0.482 0.315 2.14E−35 A24 Cxcl1 Prg4 3.70E−39 0.4007 0.421 0.254 9.19E−35 A24 Prg4 Adh41 9.82E−39 0.39197 0.667 0.538 2.44E−34 A24 Adh4 Lrg11 4.41E−38 0.30956 0.849 0.786 1.09E−33 A24 Lrg1 Hsd17b21 1.09E−37 0.32314 0.758 0.682 2.72E−33 A24 Hsd17b2 Hsd3b51 1.25E−36 0.30091 0.638 0.451 3.10E−32 A24 Hsd3b5 Hs3st3b1 3.00E−36 0.3219 0.442 0.286 7.44E−32 A24 Hs3st3b1 Rpn1 3.41E−36 0.39915 0.605 0.494 8.47E−32 A24 Rpn1 Tmem30a 9.46E−36 0.30562 0.766 0.712 2.35E−31 A24 Tmem30a Rrbp1 2.26E−35 0.29675 0.823 0.794 5.62E−31 A24 Rrbp1 Cyb5r3 9.28E−35 0.30966 0.8 0.757 2.30E−30 A24 Cyb5r3 Hnf4a1 9.32E−34 0.25495 0.85 0.799 2.31E−29 A24 Hnf4a Fos 1.67E−33 0.36319 0.654 0.54 4.16E−29 A24 Fos Abca11 3.07E−33 0.38309 0.556 0.428 7.62E−29 A24 Abca1 Cltc1 1.19E−32 0.33967 0.61 0.485 2.96E−28 A24 Cltc Qsox1 6.53E−32 0.28175 0.784 0.741 1.62E−27 A24 Qsox1 Lrp1 2.33E−31 0.48374 0.694 0.626 5.78E−27 A24 Lrp1 Mlec 2.33E−31 0.34053 0.496 0.361 5.78E−27 A24 Mlec Ssr1 3.21E−31 0.31287 0.523 0.389 7.96E−27 A24 Ssr1 Nrp11 1.23E−30 0.32998 0.426 0.278 3.05E−26 A24 Nrp1 Ostc 3.89E−30 0.30819 0.514 0.373 9.65E−26 A24 Ostc Kmo1 9.66E−30 0.2687 0.778 0.756 2.40E−25 A24 Kmo Ctnnb1 7.11E−29 0.32898 0.566 0.457 1.77E−24 A24 Ctnnb1 Uggt1 9.70E−29 0.28054 0.385 0.245 2.41E−24 A24 Uggt1 Gjb21 1.47E−28 0.2998 0.709 0.635 3.66E−24 A24 Gjb2 Uso1 2.20E−28 0.32023 0.597 0.51 5.47E−24 A24 Uso1 Slc3a1 2.88E−28 0.30744 0.378 0.24 7.15E−24 A24 Slc3a1 Efna1 5.06E−28 0.31613 0.482 0.361 1.26E−23 A24 Efna1 Usp9x 1.17E−27 0.33869 0.502 0.378 2.91E−23 A24 Usp9x Sec61b1 2.12E−27 0.30077 0.549 0.435 5.27E−23 A24 Sec61b Calu 4.28E−27 0.30047 0.407 0.276 1.06E−22 A24 Calu Ak3 4.61E−27 0.25045 0.772 0.74 1.14E−22 A24 Ak3 Nedd4 1.15E−26 0.33055 0.647 0.583 2.86E−22 A24 Nedd4 Usp4 5.04E−26 0.2959 0.476 0.347 1.25E−21 A24 Usp4 Gm54241 8.58E−26 0.26199 0.445 0.309 2.13E−21 A24 Gm5424 Dhcr24 1.11E−25 0.28238 0.857 0.827 2.77E−21 A24 Dhcr24 Rab1 1.32E−25 0.31448 0.588 0.498 3.29E−21 A24 Rab1 Eif4g11 3.05E−25 0.27629 0.745 0.715 7.57E−21 A24 Eif4g1 Acsl4 5.14E−25 0.29904 0.478 0.365 1.28E−20 A24 Acsl4 Dnajb11 1.54E−24 0.32878 0.557 0.467 3.83E−20 A24 Dnajb11 Srebf1 1.85E−24 0.31485 0.439 0.319 4.59E−20 A24 Srebf1 Arcn1 1.92E−24 0.3044 0.53 0.421 4.76E−20 A24 Arcn1 Copa 6.77E−24 0.33341 0.525 0.417 1.68E−19 A24 Copa Mug21 1.27E−23 0.31662 0.784 0.767 3.15E−19 A24 Mug2 Il6st 1.30E−23 0.3011 0.448 0.329 3.23E−19 A24 Il6st Etnk1 2.89E−23 0.31944 0.49 0.384 7.17E−19 A24 Etnk1 Prkd31 3.51E−23 0.30413 0.631 0.557 8.72E−19 A24 Prkd3 Rdx1 4.33E−23 0.27601 0.729 0.695 1.07E−18 A24 Rdx Ibtk 5.93E−23 0.2959 0.43 0.312 1.47E−18 A24 Ibtk Lgr4 1.20E−22 0.25721 0.399 0.279 2.99E−18 A24 Lgr4 Srpr 5.67E−22 0.29141 0.532 0.442 1.41E−17 A24 Srpr Lman11 6.76E−22 0.25181 0.75 0.697 1.68E−17 A24 Lman1 Edem1 1.41E−20 0.26754 0.566 0.477 3.50E−16 A24 Edem1 Pten 1.56E−20 0.26629 0.612 0.536 3.87E−16 A24 Pten Lrrc591 5.25E−20 0.26877 0.449 0.341 1.30E−15 A24 Lrrc59 Srp72 6.96E−20 0.27999 0.597 0.524 1.73E−15 A24 Srp72 Nars1 1.10E−19 0.31271 0.593 0.534 2.74E−15 A24 Nars Ptprf1 1.19E−19 0.28883 0.588 0.514 2.95E−15 A24 Ptprf Trip12 1.43E−19 0.28318 0.504 0.407 3.54E−15 A24 Trip12 Mtus1 1.55E−19 0.31246 0.563 0.485 3.85E−15 A24 Mtus1 Stard4 2.95E−19 0.29219 0.559 0.471 7.32E−15 A24 Stard4 Proz 3.55E−19 0.27997 0.622 0.56 8.83E−15 A24 Proz Txndc5 6.96E−19 0.27583 0.48 0.378 1.73E−14 A24 Txndc5 Echdc1 8.90E−19 0.28178 0.503 0.423 2.21E−14 A24 Echdc1 Gm242451 1.07E−18 0.41399 0.369 0.262 2.65E−14 A24 Gm24245 Sec31a 1.72E−18 0.2596 0.462 0.361 4.27E−14 A24 Sec31a Sh3bgrl 2.81E−18 0.26679 0.512 0.42 6.99E−14 A24 Sh3bgrl Mtss1 4.50E−18 0.25221 0.581 0.508 1.12E−13 A24 Mtss1 Sel1l 7.10E−18 0.28335 0.544 0.46 1.76E−13 A24 Sel1l Ddost 8.86E−18 0.2909 0.493 0.411 2.20E−13 A24 Ddost Slc38a10 2.68E−17 0.25566 0.449 0.354 6.66E−13 A24 Slc38a10 Nab1 5.44E−17 0.26005 0.491 0.398 1.35E−12 A24 Nab1 Nr5a2 9.20E−17 0.2599 0.403 0.305 2.28E−12 A24 Nr5a2 Met 1.57E−16 0.25118 0.434 0.344 3.91E−12 A24 Met Stt3b 1.78E−15 0.26482 0.485 0.404 4.42E−11 A24 Stt3b Atp11c 2.49E−15 0.25676 0.649 0.621 6.17E−11 A24 Atp11c Lasp1 2.85E−15 0.2608 0.361 0.268 7.09E−11 A24 Lasp1 Grlf1 5.07E−15 0.25556 0.413 0.321 1.26E−10 A24 Grlf1 Fam120a 2.45E−14 0.25828 0.51 0.444 6.09E−10 A24 Fam120a Eprs1 1.69E−12 0.25129 0.587 0.553 4.20E−08 A24 Eprs Lpgat11 2.69E−12 0.2525 0.635 0.587 6.67E−08 A24 Lpgat1 Zbtb201 5.86E−12 0.31348 0.566 0.513 1.46E−07 A24 Zbtb20 Fasn 5.64E−09 0.2699 0.449 0.394 0.0001401 A24 Fasn Cyp4a142 0 1.28082 0.991 0.5 0 A48 Cyp4a14 Mat1a2 0 0.77534 1 0.97 0 A48 Mat1a Hmgcs22 0 0.76866 1 0.977 0 A48 Hmgcs2 Apoe2  1.02E−282 0.50485 1 1  2.53E−278 A48 Apoe Ces1c2  1.85E−278 0.54878 0.999 0.984  4.59E−274 A48 Ces1c Cyp4a101  2.26E−270 0.93258 0.991 0.643  5.62E−266 A48 Cyp4a10 Chchd102  1.01E−265 0.75168 0.995 0.925  2.50E−261 A48 Chchd10 Apoc21  4.27E−263 0.86385 0.98 0.8  1.06E−258 A48 Apoc2 Mfsd2a2  8.03E−247 0.66138 0.731 0.203  1.99E−242 A48 Mfsd2a Ttc362  5.87E−246 0.56379 0.996 0.93  1.46E−241 A48 Ttc36 Angptl32  1.51E−240 0.61108 0.995 0.946  3.74E−236 A48 Angptl3 Apoh2  2.05E−235 0.46279 0.998 0.979  5.10E−231 A48 Apoh Dbp  5.52E−234 0.28956 0.52 0.091  1.37E−229 A48 Dbp Ahsg1  5.89E−227 0.35916 1 0.999  1.46E−222 A48 Ahsg Vtn1  2.03E−225 0.52281 1 0.98  5.04E−221 A48 Vtn Rgs16  5.76E−225 0.45446 0.601 0.138  1.43E−220 A48 Rgs16 Retsat2  2.28E−218 0.70957 0.988 0.827  5.66E−214 A48 Retsat Abcd2  2.96E−203 0.2813 0.473 0.087  7.35E−199 A48 Abcd2 Agt1  5.52E−203 0.57953 0.981 0.814  1.37E−198 A48 Agt Herpud11  1.06E−202 0.60438 0.985 0.795  2.64E−198 A48 Herpud1 Aldob  1.64E−196 0.4375 1 0.996  4.06E−192 A48 Aldob Serping11  3.48E−195 0.57771 0.987 0.863  8.63E−191 A48 Serping1 Reep61  1.30E−193 0.62329 0.967 0.791  3.24E−189 A48 Reep6 Apoa51  1.41E−191 0.44835 0.998 0.961  3.49E−187 A48 Apoa5 Decr12  3.46E−191 0.56691 0.96 0.678  8.60E−187 A48 Decr1 Slc25a472  1.27E−188 0.61748 0.992 0.917  3.16E−184 A48 Slc25a47 F2  2.67E−188 0.39515 0.999 0.969  6.63E−184 A48 F2 Rdh72  6.84E−187 0.46844 0.996 0.958  1.70E−182 A48 Rdh7 Hrg1  3.57E−183 0.53157 0.987 0.834  8.86E−179 A48 Hrg Rbp41  4.56E−183 0.39421 1 0.997  1.13E−178 A48 Rbp4 Tef  4.84E−177 0.33942 0.651 0.192  1.20E−172 A48 Tef Slco1a4  2.11E−176 0.50909 0.77 0.291  5.23E−172 A48 Slco1a4 Gc  3.39E−175 0.29789 1 0.998  8.41E−171 A48 Gc Gm6484  3.94E−173 0.41077 0.627 0.191  9.79E−169 A48 Gm6484 Gm23935  1.27E−167 0.47384 0.997 0.93  3.15E−163 A48 Gm23935 Ugt2b52  3.54E−167 0.43882 0.996 0.942  8.78E−163 A48 Ugt2b5 Ttr2  2.12E−165 0.42249 1 0.999  5.26E−161 A48 Ttr Rpl38  1.26E−162 0.3322 0.596 0.173  3.14E−158 A48 Rpl38 St3gal52  9.27E−162 0.55493 0.914 0.537  2.30E−157 A48 St3gal5 Lcat1  4.41E−155 0.50535 0.973 0.77  1.10E−150 A48 Lcat Atp5h2  8.78E−153 0.59775 0.933 0.64  2.18E−148 A48 Atp5h Apoc32  4.46E−151 0.40698 1 0.977  1.11E−146 A48 Apoc3 Cp  1.69E−147 0.42739 0.995 0.947  4.21E−143 A48 Cp Plin51  4.30E−146 0.3985 0.788 0.332  1.07E−141 A48 Plin5 Prodh21  2.43E−145 0.50547 0.918 0.598  6.02E−141 A48 Prodh2 Oaf1  3.43E−145 0.50208 0.969 0.783  8.51E−141 A48 Oaf Scand1  3.53E−145 0.27068 0.579 0.175  8.77E−141 A48 Scand1 Khk2  6.78E−145 0.52025 0.982 0.855  1.68E−140 A48 Khk Hmgcl2  1.35E−144 0.55008 0.956 0.723  3.36E−140 A48 Hmgcl Lims2  6.42E−144 0.37612 0.679 0.253  1.59E−139 A48 Lims2 Pnpla21  9.86E−144 0.3465 0.687 0.253  2.45E−139 A48 Pnpla2 Sult1a11  4.81E−142 0.48266 0.963 0.718  1.20E−137 A48 Sult1a1 Fth1  1.45E−141 0.37501 0.996 0.975  3.60E−137 A48 Fth1 Lpin11  9.79E−141 0.51496 0.736 0.315  2.43E−136 A48 Lpin1 Hdac111  4.34E−139 0.35573 0.713 0.277  1.08E−134 A48 Hdac11 Syvn1  4.46E−139 0.30412 0.603 0.201  1.11E−134 A48 Syvn1 Ttpa  1.70E−138 0.44315 0.991 0.876  4.23E−134 A48 Ttpa Nr1i32  3.96E−138 0.47586 0.814 0.371  9.85E−134 A48 Nr1i3 Fkbp51  1.26E−136 0.25723 0.54 0.158  3.12E−132 A48 Fkbp5 Ephx21  6.88E−135 0.38687 0.993 0.919  1.71E−130 A48 Ephx2 Snord1181  9.71E−135 0.47712 0.766 0.324  2.41E−130 A48 Snord118 Slc27a51  3.81E−134 0.40618 0.987 0.885  9.45E−130 A48 Slc27a5 Ces1b  1.19E−132 0.48295 0.838 0.445  2.95E−128 A48 Ces1b Ndrg21  1.81E−132 0.3482 1 0.939  4.50E−128 A48 Ndrg2 Cox8a2  3.15E−131 0.552 0.89 0.599  7.83E−127 A48 Cox8a Cyp2a12  1.00E−129 0.46643 0.981 0.879  2.49E−125 A48 Cyp2a12 Cyp3a252  2.18E−129 0.36073 0.995 0.902  5.41E−125 A48 Cyp3a25 Ambp  5.70E−128 0.28598 1 0.991  1.42E−123 A48 Ambp Pabpc1  5.17E−127 0.4782 0.912 0.629  1.28E−122 A48 Pabpc1 Mlycd1  9.54E−127 0.43784 0.893 0.5  2.37E−122 A48 Mlycd F101  1.50E−125 0.39272 0.989 0.886  3.73E−121 A48 F10 Gys21  2.76E−124 0.42306 0.784 0.376  6.84E−120 A48 Gys2 Cdo11  1.19E−123 0.39707 0.997 0.956  2.96E−119 A48 Cdo1 Echs11  2.01E−123 0.46487 0.971 0.806  5.00E−119 A48 Echs1 Bnip32  3.06E−123 0.46203 0.876 0.529  7.61E−119 A48 Bnip3 Slc37a41  4.81E−123 0.44612 0.858 0.484  1.19E−118 A48 Slc37a4 Tmbim61  1.33E−122 0.37131 0.996 0.943  3.30E−118 A48 Tmbim6 Bfar  3.12E−122 0.30801 0.742 0.306  7.75E−118 A48 Bfar Ube2r21  4.52E−122 0.4423 0.884 0.54  1.12E−117 A48 Ube2r2 Abcb41  2.99E−121 0.44252 0.956 0.688  7.42E−117 A48 Abcb4 Grn1  6.37E−120 0.43104 0.844 0.449  1.58E−115 A48 Grn Slc25a102  3.22E−119 0.43127 0.877 0.526  8.00E−115 A48 Slc25a10 Hpx1  7.59E−118 0.38511 0.999 0.997  1.89E−113 A48 Hpx Vnn3  4.99E−116 0.30084 0.684 0.275  1.24E−111 A48 Vnn3 Fcgrt1  2.63E−115 0.40844 0.91 0.576  6.53E−111 A48 Fcgrt Fah1  8.72E−115 0.39129 0.974 0.821  2.17E−110 A48 Fah Atp5b  1.69E−114 0.32811 0.997 0.94  4.19E−110 A48 Atp5b Amy12  4.53E−114 0.42158 0.943 0.66  1.13E−109 A48 Amy1 Gstt3  3.70E−113 0.33837 0.737 0.312  9.19E−109 A48 Gstt3 Ech11  1.29E−112 0.41801 0.98 0.828  3.21E−108 A48 Ech1 Hsd17b131  1.32E−112 0.62207 0.934 0.741  3.29E−108 A48 Hsd17b13 Serpina3m1  6.99E−112 0.40339 0.949 0.749  1.74E−107 A48 Serpina3m Serpina1d2  2.32E−111 0.3053 0.997 0.977  5.77E−107 A48 Serpina1d Decr21  2.53E−109 0.41288 0.92 0.644  6.29E−105 A48 Decr2 Hspa82  5.67E−109 0.41074 0.952 0.731  1.41E−104 A48 Hspa8 Gltscr2  1.30E−108 0.34321 0.83 0.435  3.24E−104 A48 Gltscr2 Slc25a20  2.03E−108 0.38754 0.877 0.508  5.03E−104 A48 Slc25a20 Abhd14b1  5.35E−108 0.40591 0.885 0.554  1.33E−103 A48 Abhd14b Cebpb2  2.85E−107 0.36838 0.815 0.414  7.09E−103 A48 Cebpb Ahcy1  6.37E−107 0.33998 0.988 0.875  1.58E−102 A48 Ahcy F12  9.50E−107 0.38801 0.966 0.803  2.36E−102 A48 F12 Cox5a1  2.15E−106 0.41972 0.938 0.693  5.34E−102 A48 Cox5a Tcea31  3.05E−106 0.39376 0.825 0.448  7.58E−102 A48 Tcea3 Tmbim41  6.73E−106 0.36929 0.784 0.407  1.67E−101 A48 Tmbim4 Acad11  1.16E−105 0.38509 0.896 0.583  2.88E−101 A48 Acad11 Gabarap1  8.50E−105 0.40143 0.956 0.75  2.11E−100 A48 Gabarap Aldh9a1  9.77E−105 0.38255 0.964 0.772  2.43E−100 A48 Aldh9a1 Ddb1  2.16E−103 0.35442 0.83 0.452 5.37E−99 A48 Ddb1 P4hb2  5.46E−103 0.29806 0.995 0.942 1.36E−98 A48 P4hb Yipf3  1.81E−102 0.27846 0.68 0.291 4.50E−98 A48 Yipf3 Sh3glb1  9.56E−102 0.30436 0.695 0.306 2.37E−97 A48 Sh3glb1 Rpl4  2.39E−101 0.32886 0.987 0.912 5.93E−97 A48 Rpl4 Ctsh1  2.95E−101 0.42242 0.945 0.72 7.32E−97 A48 Ctsh Apoa41  1.97E−100 0.49471 0.778 0.4 4.90E−96 A48 Apoa4 Mgll  3.72E−100 0.36511 0.844 0.477 9.23E−96 A48 Mgll Ppara1  6.73E−100 0.33932 0.831 0.443 1.67E−95 A48 Ppara 1600002H07Rik 1.17E−98 0.30158 0.736 0.353 2.91E−94 A48 1600002H07Rik G0s21 1.31E−98 0.38797 0.692 0.32 3.26E−94 A48 G0s2 Cox6a12 1.81E−98 0.37182 0.987 0.854 4.49E−94 A48 Cox6a1 Igfbp4 6.46E−98 0.33954 0.99 0.875 1.60E−93 A48 Igfbp4 C4b1 2.60E−97 0.39891 0.975 0.876 6.46E−93 A48 C4b Sdhc 2.46E−96 0.3865 0.91 0.645 6.10E−92 A48 Sdhc Apoc42 3.94E−96 0.40964 0.998 0.965 9.79E−92 A48 Apoc4 Serpinf1 4.30E−96 0.35652 0.976 0.855 1.07E−91 A48 Serpinf1 Wbp1l1 7.44E−96 0.38751 0.91 0.648 1.85E−91 A48 Wbp1l Aldoa 1.89E−95 0.27774 0.719 0.329 4.70E−91 A48 Aldoa Atp5k1 2.67E−95 0.38427 0.935 0.664 6.63E−91 A48 Atp5k Aspdh 5.69E−95 0.32171 0.776 0.397 1.41E−90 A48 Aspdh Gm2a 4.55E−94 0.34919 0.827 0.459 1.13E−89 A48 Gm2a Etnppl2 1.17E−93 0.52531 0.866 0.587 2.89E−89 A48 Etnppl Etfb1 8.54E−93 0.30917 0.996 0.928 2.12E−88 A48 Etfb Sec14l21 1.30E−92 0.35236 0.98 0.835 3.23E−88 A48 Sec14l2 Camk2n11 2.32E−92 0.27301 0.691 0.315 5.77E−88 A48 Camk2n1 Slc10a11 2.86E−92 0.37533 0.984 0.84 7.10E−88 A48 Slc10a1 Ifnar2 6.13E−92 0.27491 0.731 0.34 1.52E−87 A48 Ifnar2 Cpt2 8.07E−92 0.32669 0.807 0.437 2.00E−87 A48 Cpt2 Azgp1 2.23E−91 0.25201 0.997 0.966 5.53E−87 A48 Azgp1 Uroc1 1.35E−90 0.40743 0.914 0.637 3.34E−86 A48 Uroc1 Pbld11 6.93E−90 0.34533 0.881 0.566 1.72E−85 A48 Pbld1 Brap 1.06E−89 0.31593 0.829 0.465 2.62E−85 A48 Brap Shmt11 1.20E−89 0.34796 0.882 0.556 2.98E−85 A48 Shmt1 Slc27a2 1.39E−89 0.31391 0.996 0.945 3.44E−85 A48 Slc27a2 Asgr21 7.88E−89 0.34851 0.879 0.552 1.96E−84 A48 Asgr2 Aco2 3.32E−88 0.32671 0.846 0.507 8.24E−84 A48 Aco2 Ctsd 1.28E−87 0.35447 0.916 0.642 3.17E−83 A48 Ctsd Cyp3a112 3.21E−87 0.39704 1 0.995 7.98E−83 A48 Cyp3a11 Sdhd2 4.40E−87 0.43472 0.891 0.655 1.09E−82 A48 Sdhd 0610005C13Rik1 6.63E−86 0.33556 0.944 0.665 1.65E−81 A48 0610005C13Rik Slc40a11 9.34E−86 0.27255 0.744 0.367 2.32E−81 A48 Slc40a1 Cyp2c441 1.12E−85 0.41494 0.924 0.692 2.77E−81 A48 Cyp2c44 Lamp11 1.61E−85 0.32739 0.982 0.877 4.01E−81 A48 Lamp1 Creb3l3 5.60E−85 0.33049 0.971 0.818 1.39E−80 A48 Creb3l3 Pigr 1.16E−84 0.40014 0.977 0.945 2.89E−80 A48 Pigr Apoc12 4.87E−84 0.29282 1 0.992 1.21E−79 A48 Apoc1 Smlr11 5.67E−84 0.25158 0.68 0.317 1.41E−79 A48 Smlr1 Snx3 7.63E−84 0.2563 0.693 0.331 1.89E−79 A48 Snx3 Atp5g31 1.55E−83 0.32884 0.985 0.888 3.85E−79 A48 Atp5g3 Cyp2d26 4.14E−83 0.30505 0.982 0.897 1.03E−78 A48 Cyp2d26 Klf9 4.69E−83 0.33261 0.862 0.549 1.17E−78 A48 Klf9 Eci2 5.28E−83 0.32811 0.944 0.697 1.31E−78 A48 Eci2 Slc2a21 7.42E−83 0.35696 0.824 0.485 1.84E−78 A48 Slc2a2 Acot12 6.96E−82 0.27848 0.825 0.454 1.73E−77 A48 Acot12 Tmem120a 1.04E−81 0.2525 0.708 0.343 2.59E−77 A48 Tmem120a Pglyrp2 6.41E−81 0.30742 0.754 0.402 1.59E−76 A48 Pglyrp2 Abcc3 1.62E−80 0.35577 0.859 0.549 4.03E−76 A48 Abcc3 Fam195a1 4.52E−80 0.28611 0.726 0.359 1.12E−75 A48 Fam195a Ctsa 8.45E−80 0.25496 0.731 0.36 2.10E−75 A48 Ctsa Oplah 1.28E−79 0.30336 0.805 0.457 3.19E−75 A48 Oplah Acat11 4.32E−79 0.30733 0.978 0.842 1.07E−74 A48 Acat1 Park71 3.18E−78 0.34371 0.953 0.774 7.89E−74 A48 Park7 Pbld2 4.10E−78 0.31208 0.891 0.58 1.02E−73 A48 Pbld2 Serpina3n1 9.63E−78 0.31814 0.902 0.626 2.39E−73 A48 Serpina3n Serinc31 3.42E−77 0.28974 0.793 0.452 8.48E−73 A48 Serinc3 Pitpnb 8.76E−77 0.26612 0.795 0.431 2.18E−72 A48 Pitpnb Usmg52 9.41E−77 0.37613 0.755 0.419 2.34E−72 A48 Usmg5 Ninj11 9.74E−77 0.34623 0.874 0.587 2.42E−72 A48 Ninj1 Hsd17b102 2.43E−76 0.40473 0.927 0.686 6.03E−72 A48 Hsd17b10 Eef1d 6.80E−75 0.2572 0.795 0.434 1.69E−70 A48 Eef1d Lipa1 2.40E−74 0.31862 0.904 0.63 5.96E−70 A48 Lipa Agpat6 3.14E−74 0.28948 0.884 0.558 7.81E−70 A48 Agpat6 Pim31 3.82E−74 0.31374 0.845 0.52 9.48E−70 A48 Pim3 Pcx 5.84E−74 0.31598 0.912 0.66 1.45E−69 A48 Pcx Creg11 3.96E−73 0.29796 0.993 0.917 9.83E−69 A48 Creg1 Gcdh1 4.36E−73 0.28849 0.977 0.848 1.08E−68 A48 Gcdh Atp5d1 1.54E−72 0.30761 0.935 0.694 3.81E−68 A48 Atp5d Gfra11 1.91E−72 0.28896 0.867 0.539 4.74E−68 A48 Gfra1 Pck11 2.03E−72 0.35008 0.999 0.974 5.03E−68 A48 Pck1 Gstt2 1.93E−71 0.25927 0.754 0.398 4.80E−67 A48 Gstt2 Sord1 3.59E−71 0.30187 0.987 0.917 8.92E−67 A48 Sord Tmem371 7.54E−71 0.26106 0.786 0.429 1.87E−66 A48 Tmem37 Pla2g12b 8.56E−71 0.27883 0.798 0.457 2.13E−66 A48 Pla2g12b Ndufb22 1.82E−70 0.3484 0.888 0.589 4.53E−66 A48 Ndufb2 Atf5 2.73E−70 0.31719 0.909 0.649 6.78E−66 A48 Atf5 Sfxn1 2.87E−70 0.32927 0.822 0.522 7.13E−66 A48 Sfxn1 Glrx52 3.18E−70 0.29996 0.886 0.568 7.89E−66 A48 Glrx5 Atp5j1 2.90E−69 0.35068 0.916 0.73 7.19E−65 A48 Atp5j Ggnbp2 3.08E−69 0.25778 0.818 0.458 7.65E−65 A48 Ggnbp2 Furin 4.55E−69 0.28056 0.781 0.445 1.13E−64 A48 Furin Ndufb101 7.41E−69 0.31642 0.907 0.669 1.84E−64 A48 Ndufb10 Dhrs41 1.15E−68 0.27653 0.94 0.671 2.87E−64 A48 Dhrs4 Sec61a1 1.50E−68 0.28991 0.825 0.513 3.72E−64 A48 Sec61a1 Zfp91 1.51E−68 0.27537 0.855 0.531 3.75E−64 A48 Zfp91 D17Wsu92e 1.81E−68 0.28265 0.909 0.62 4.49E−64 A48 D17Wsu92e Sult1d12 2.07E−68 0.4399 0.936 0.68 5.14E−64 A48 Sult1d1 Mst1 3.99E−68 0.27754 0.81 0.489 9.91E−64 A48 Mst1 Igf1 7.06E−68 0.30268 0.985 0.902 1.75E−63 A48 Igf1 Acadvl 8.03E−68 0.2803 0.959 0.782 1.99E−63 A48 Acadvl Hgfac 1.41E−67 0.26562 0.786 0.457 3.49E−63 A48 Hgfac 11-Mar 1.82E−67 0.28124 0.984 0.869 4.51E−63 A48 1-Mar Tgoln1 4.48E−67 0.30552 0.891 0.602 1.11E−62 A48 Tgoln1 Upb11 4.61E−67 0.30588 0.945 0.746 1.14E−62 A48 Upb1 Acbd51 7.35E−67 0.28409 0.943 0.711 1.82E−62 A48 Acbd5 Sds2 2.26E−66 0.55395 0.799 0.612 5.62E−62 A48 Sds Map2k2 2.40E−66 0.25507 0.832 0.517 5.96E−62 A48 Map2k2 Ndufs71 2.84E−66 0.25451 0.847 0.51 7.05E−62 A48 Ndufs7 Dcxr2 3.22E−66 0.29887 0.884 0.591 7.99E−62 A48 Dcxr Gpt1 3.35E−66 0.2881 0.94 0.737 8.32E−62 A48 Gpt Gpld1 6.68E−66 0.28871 0.877 0.595 1.66E−61 A48 Gpld1 1100001G20Rik1 7.71E−66 0.34154 0.993 0.968 1.91E−61 A48 1100001G20Rik Ndufs81 2.39E−65 0.31488 0.854 0.581 5.94E−61 A48 Ndufs8 Abca6 5.35E−65 0.28403 0.849 0.548 1.33E−60 A48 Abca6 Actn4 4.59E−64 0.25336 0.789 0.465 1.14E−59 A48 Actn4 Gchfr2 2.18E−63 0.32395 0.953 0.727 5.42E−59 A48 Gchfr Mia3 6.64E−63 0.28475 0.91 0.64 1.65E−58 A48 Mia3 Cd1d11 8.52E−63 0.29268 0.887 0.611 2.11E−58 A48 Cd1d1 Tmem176b1 9.86E−63 0.28825 0.89 0.63 2.45E−58 A48 Tmem176b Lpin21 1.01E−62 0.30413 0.921 0.653 2.52E−58 A48 Lpin2 Pccb 1.17E−62 0.28017 0.901 0.642 2.90E−58 A48 Pccb Cideb2 1.52E−62 0.31595 0.892 0.65 3.79E−58 A48 Cideb Itih1 2.19E−62 0.28878 0.974 0.819 5.45E−58 A48 Itih1 B2m2 2.44E−62 0.25723 0.997 0.949 6.06E−58 A48 B2m Maob 5.02E−62 0.28848 0.889 0.597 1.25E−57 A48 Maob Slc25a39 6.32E−62 0.29589 0.938 0.762 1.57E−57 A48 Slc25a39 Acadl 9.46E−62 0.2603 0.916 0.643 2.35E−57 A48 Acadl Hadh1 1.41E−61 0.27999 0.908 0.641 3.49E−57 A48 Hadh Akr1c191 5.83E−61 0.29518 0.821 0.507 1.45E−56 A48 Akr1c19 Os9 1.17E−60 0.26825 0.911 0.673 2.90E−56 A48 Os9 Pemt1 1.39E−60 0.31675 0.948 0.754 3.46E−56 A48 Pemt Hsbp11 1.15E−59 0.25477 0.792 0.495 2.86E−55 A48 Hsbp1 Serpinf2 2.36E−59 0.26266 0.966 0.847 5.86E−55 A48 Serpinf2 Ndufa131 6.13E−59 0.28644 0.959 0.769 1.52E−54 A48 Ndufa13 Gsto1 6.52E−59 0.27994 0.818 0.518 1.62E−54 A48 Gsto1 Ubxn4 2.22E−58 0.25605 0.893 0.601 5.52E−54 A48 Ubxn4 Slc25a13 2.47E−58 0.26362 0.924 0.668 6.14E−54 A48 Slc25a13 Hadha 3.06E−58 0.279 0.943 0.743 7.60E−54 A48 Hadha Surf4 3.88E−58 0.25226 0.873 0.578 9.64E−54 A48 Surf4 Hal1 4.19E−58 0.38266 0.908 0.741 1.04E−53 A48 Hal Akr1d11 1.29E−57 0.2648 0.852 0.543 3.22E−53 A48 Akr1d1 Rabac12 5.41E−56 0.25087 0.807 0.498 1.34E−51 A48 Rabac1 Tspo1 7.02E−56 0.26601 0.784 0.477 1.74E−51 A48 Tspo Mttp 9.90E−56 0.2617 0.933 0.709 2.46E−51 A48 Mttp Ctage5 2.71E−55 0.27451 0.941 0.698 6.74E−51 A48 Ctage5 Agpat3 3.06E−55 0.2526 0.874 0.617 7.61E−51 A48 Agpat3 Gamt1 3.37E−55 0.26806 0.841 0.564 8.36E−51 A48 Gamt Dgat21 3.63E−55 0.2637 0.947 0.753 9.02E−51 A48 Dgat2 Sardh 7.35E−53 0.27838 0.959 0.829 1.82E−48 A48 Sardh Asl1 2.33E−51 0.33611 0.953 0.801 5.79E−47 A48 Asl Acsl12 5.59E−51 0.25453 0.978 0.895 1.39E−46 A48 Acsl1 Ccs1 9.34E−50 0.26432 0.895 0.655 2.32E−45 A48 Ccs BC089597 1.42E−49 0.25099 0.813 0.516 3.52E−45 A48 BC089597 Por2 5.03E−49 0.28933 0.921 0.688 1.25E−44 A48 Por Uqcrfs1 6.79E−48 0.25793 0.949 0.781 1.69E−43 A48 Uqcrfs1 Hagh1 4.03E−47 0.28738 0.959 0.834 1.00E−42 A48 Hagh Tmem14c1 5.76E−47 0.25067 0.837 0.561 1.43E−42 A48 Tmem14c Dak 5.90E−47 0.29663 0.852 0.575 1.47E−42 A48 Dak Leap22 2.60E−44 0.33563 0.833 0.576 6.45E−40 A48 Leap2 Cpt1a 1.94E−43 0.26499 0.896 0.681 4.81E−39 A48 Cpt1a Mpc22 1.37E−42 0.28745 0.953 0.826 3.40E−38 A48 Mpc2 Cd3021 6.25E−40 0.27124 0.956 0.844 1.55E−35 A48 Cd302 Rps27l2 8.74E−39 0.28686 0.924 0.795 2.17E−34 A48 Rps27l Cyp2f21 3.99E−31 0.29608 0.912 0.833 9.91E−27 A48 Cyp2f2 Slc7a2 3.98E−30 0.25021 0.921 0.758 9.87E−26 A48 Slc7a2 Glul 2.05E−13 0.54015 0.308 0.18 5.09E−09 A48 Glul Apoc13  1.14E−259 0.54953 1 0.992  2.84E−255 A96 Apoc1 Cyp4a143  2.66E−250 0.97024 0.975 0.511  6.60E−246 A96 Cyp4a14 Cyp4a102  2.15E−216 0.86815 0.974 0.651  5.34E−212 A96 Cyp4a10 Mat1a3  3.10E−210 0.59668 1 0.97  7.70E−206 A96 Mat1a Angptl33  5.10E−206 0.56056 0.998 0.946  1.27E−201 A96 Angptl3 Cdo12  3.07E−182 0.50859 0.998 0.957  7.61E−178 A96 Cdo1 Apoa22  2.85E−177 0.34475 1 0.999  7.07E−173 A96 Apoa2 Zfp683  2.01E−176 0.41844 0.476 0.092  4.99E−172 A96 Zfp683 Apoe3  2.87E−148 0.31614 1 1  7.13E−144 A96 Apoe Chchd103  1.38E−138 0.47684 0.994 0.927  3.43E−134 A96 Chchd10 Ttr3  2.28E−137 0.31745 1 0.999  5.66E−133 A96 Ttr Ttpa1  4.82E−129 0.49263 0.98 0.879  1.20E−124 A96 Ttpa Scd12  2.34E−118 0.52026 0.989 0.926  5.82E−114 A96 Scd1 Ubc2  2.86E−109 0.48097 0.968 0.839  7.10E−105 A96 Ubc Apoh3  2.32E−107 0.30846 0.998 0.979  5.76E−103 A96 Apoh Ces1d1  9.98E−105 0.45085 0.977 0.905  2.48E−100 A96 Ces1d Apoc33  1.84E−102 0.33815 1 0.978 4.56E−98 A96 Apoc3 Ces1c3 8.24E−97 0.29829 1 0.985 2.05E−92 A96 Ces1e Hmgcs23 2.29E−95 0.30409 0.996 0.977 5.70E−91 A96 Hmgcs2 Slco1b21 3.01E−92 0.51568 0.998 0.929 7.48E−88 A96 Slco1b2 Cyp8b12 6.15E−88 0.51669 0.897 0.691 1.53E−83 A96 Cyp8b1 Hamp2 4.13E−86 0.54886 0.92 0.788 1.03E−81 A96 Hamp Slc27a21 7.10E−80 0.32514 0.988 0.947 1.76E−75 A96 Slc27a2 Hspa83 1.35E−77 0.41417 0.905 0.741 3.34E−73 A96 Hspa8 Mettl7b1 3.18E−76 0.37013 0.949 0.866 7.90E−72 A96 Mettl7b Cyp3a113 1.94E−75 0.275 0.999 0.995 4.82E−71 A96 Cyp3a11 Crot1 7.79E−75 0.31433 0.989 0.942 1.94E−70 A96 Crot Cyp2c292 1.44E−68 0.55102 0.962 0.85 3.59E−64 A96 Cyp2c29 Acbd52 3.67E−64 0.3903 0.87 0.725 9.12E−60 A96 Acbd5 Acsl13 2.22E−63 0.3297 0.977 0.897 5.52E−59 A96 Acsl1 Sult1a12 2.88E−62 0.38498 0.881 0.733 7.15E−58 A96 Sult1a1 Aldh2 6.54E−62 0.28252 0.995 0.968 1.62E−57 A96 Aldh2 Retsat3 2.39E−61 0.36555 0.957 0.834 5.92E−57 A96 Retsat Abcb42 3.19E−61 0.38995 0.878 0.704 7.92E−57 A96 Abcb4 Ndrg22 1.13E−60 0.27001 0.985 0.942 2.81E−56 A96 Ndrg2 Aldh3a22 3.23E−60 0.56589 0.687 0.451 8.02E−56 A96 Aldh3a2 Atp5k2 9.30E−60 0.37147 0.837 0.682 2.31E−55 A96 Atp5k Amy13 2.54E−58 0.38615 0.831 0.681 6.31E−54 A96 Amy1 Igfbp41 2.23E−56 0.29578 0.964 0.881 5.53E−52 A96 Igfbp4 Chpt11 2.52E−56 0.3802 0.848 0.694 6.27E−52 A96 Chpt1 Pex11a1 4.35E−56 0.44625 0.7 0.484 1.08E−51 A96 Pex11a Hhex1 7.20E−54 0.35579 0.543 0.313 1.79E−49 A96 Hhex Sult1d13 2.09E−51 0.38992 0.855 0.696 5.20E−47 A96 Sult1d1 Atp5h3 1.30E−50 0.31445 0.848 0.657 3.24E−46 A96 Atp5h Cyp3a253 5.89E−50 0.2703 0.981 0.905 1.46E−45 A96 Cyp3a25 Lipa2 1.77E−49 0.35594 0.791 0.651 4.41E−45 A96 Lipa Cyp2e12 4.42E−49 0.51183 0.93 0.809 1.10E−44 A96 Cyp2e1 Prlr 2.34E−48 0.34641 0.574 0.359 5.82E−44 A96 Prlr Clpx1 3.44E−48 0.3254 0.884 0.764 8.54E−44 A96 Clpx Tmem56 4.52E−47 0.33425 0.812 0.643 1.12E−42 A96 Tmem56 Insig22 1.46E−46 0.28539 0.928 0.818 3.63E−42 A96 Insig2 Hrg2 6.03E−46 0.28054 0.923 0.845 1.50E−41 A96 Hrg Ube2r22 1.09E−45 0.33818 0.747 0.565 2.70E−41 A96 Ube2r2 Ppp2r5a1 3.21E−45 0.35054 0.764 0.615 7.96E−41 A96 Ppp2r5a Nr1i33 6.04E−44 0.34813 0.625 0.405 1.50E−39 A96 Nr1i3 Cox6a13 9.03E−44 0.27455 0.943 0.862 2.24E−39 A96 Cox6a1 Creg12 1.75E−43 0.25169 0.985 0.919 4.34E−39 A96 Creg1 Acaa1b2 3.05E−43 0.28198 0.986 0.919 7.56E−39 A96 Acaa1b Cyp7a1 1.08E−42 0.37883 0.398 0.199 2.68E−38 A96 Cyp7a1 Cyp2c542 1.49E−42 0.34469 0.86 0.726 3.70E−38 A96 Cyp2c54 Cyp2c502 4.24E−42 0.32419 0.943 0.847 1.05E−37 A96 Cyp2c50 Snord1182 9.05E−42 0.37824 0.564 0.36 2.25E−37 A96 Snord118 Asl2 9.71E−42 0.27504 0.896 0.811 2.41E−37 A96 Asl Csad2 9.95E−42 0.42065 0.843 0.684 2.47E−37 A96 Csad Sc4mol2 2.31E−41 0.33609 0.781 0.631 5.74E−37 A96 Sc4mol Igfbp13 2.40E−41 0.26025 0.826 0.691 5.95E−37 A96 Igfbp1 Gabarapl11 6.61E−41 0.29324 0.881 0.78 1.64E−36 A96 Gabarapl1 Tsc22d3 8.65E−41 0.33625 0.534 0.338 2.15E−36 A96 Tsc22d3 Acot11 1.16E−40 0.31059 0.459 0.257 2.88E−36 A96 Acot1 Gyk 2.01E−40 0.3134 0.616 0.441 5.00E−36 A96 Gyk Decr22 3.24E−40 0.30175 0.813 0.664 8.03E−36 A96 Decr2 Cth1 3.77E−40 0.29664 0.944 0.826 9.37E−36 A96 Cth Pon12 4.32E−40 0.28987 0.965 0.888 1.07E−35 A96 Pon1 Cd36 9.83E−40 0.31288 0.299 0.131 2.44E−35 A96 Cd36 Aplp2 1.81E−39 0.29028 0.826 0.67 4.48E−35 A96 Aplp2 Agpat61 2.42E−38 0.31428 0.743 0.584 6.01E−34 A96 Agpat6 Agt2 2.70E−38 0.25501 0.912 0.827 6.71E−34 A96 Agt Hmgcl3 1.80E−37 0.27438 0.871 0.739 4.47E−33 A96 Hmgcl Gstt31 3.07E−37 0.30258 0.541 0.347 7.61E−33 A96 Gstt3 Aqp91 3.47E−37 0.31777 0.801 0.664 8.62E−33 A96 Aqp9 Akr1d12 6.11E−37 0.29936 0.721 0.567 1.52E−32 A96 Akr1d1 Slc4a41 7.42E−37 0.29765 0.609 0.42 1.84E−32 A96 Slc4a4 Ptms1 8.05E−37 0.28625 0.806 0.71 2.00E−32 A96 Ptms Rgn2 9.16E−37 0.36863 0.899 0.786 2.27E−32 A96 Rgn Lcat2 9.19E−37 0.26158 0.886 0.786 2.28E−32 A96 Leaf Hpgd1 1.45E−36 0.34118 0.588 0.41 3.59E−32 A96 Hpgd Hmgcs11 1.88E−36 0.32515 0.858 0.718 4.67E−32 A96 Hmgcs1 Rdh16 2.69E−36 0.34767 0.494 0.31 6.69E−32 A96 Rdh16 Cyp2c372 2.78E−36 0.41436 0.71 0.521 6.89E−32 A96 Cyp2c37 Tob11 1.03E−35 0.29582 0.649 0.487 2.55E−31 A96 Tobi Kif1b 2.07E−35 0.2961 0.686 0.507 5.15E−31 A96 Kif1b Bnip33 3.84E−35 0.32084 0.716 0.558 9.53E−31 A96 Bnip3 Ndufa31 4.91E−35 0.27429 0.737 0.598 1.22E−30 A96 Ndufa3 Apoc22 5.09E−35 0.27811 0.901 0.815 1.26E−30 A96 Apoc2 Aldh9a11 7.77E−35 0.25848 0.884 0.786 1.93E−30 A96 Aldh9a1 Cpt1a1 4.44E−34 0.26256 0.837 0.693 1.10E−29 A96 Cpt1a Hsd17b7 7.40E−34 0.30279 0.56 0.386 1.84E−29 A96 Hsd17b7 Acat12 7.72E−34 0.2558 0.917 0.852 1.92E−29 A96 Acat1 D4Wsu53e 8.98E−34 0.29281 0.597 0.413 2.23E−29 A96 D4Wsu53e Cox5a2 9.78E−34 0.27283 0.813 0.715 2.43E−29 A96 Cox5a Gsta21 1.28E−33 0.31098 0.522 0.356 3.17E−29 A96 Gsta2 Cxcl121 1.54E−33 0.28215 0.635 0.48 3.82E−29 A96 Cxcl12 Baat1 1.66E−33 0.27278 0.862 0.769 4.13E−29 A96 Baat Cyp2c681 1.69E−33 0.29308 0.695 0.527 4.20E−29 A96 Cyp2c68 Hsd17b103 4.80E−33 0.2802 0.841 0.702 1.19E−28 A96 Hsd17b10 Ndufa72 7.78E−33 0.26 0.818 0.695 1.93E−28 A96 Ndufa7 Rdx2 1.06E−32 0.25662 0.824 0.683 2.63E−28 A96 Rdx Gas51 1.39E−32 0.28228 0.68 0.525 3.46E−28 A96 Gas5 G6pc1 2.86E−32 0.25415 0.86 0.728 7.09E−28 A96 G6pc Cpeb4 3.54E−32 0.3011 0.527 0.357 8.79E−28 A96 Cpeb4 Tgoln11 3.58E−32 0.28089 0.756 0.626 8.89E−28 A96 Tgoln1 Tmed51 4.26E−32 0.25232 0.714 0.569 1.06E−27 A96 Tmed5 Por3 4.35E−32 0.28673 0.858 0.701 1.08E−27 A96 Por Abcc31 9.20E−32 0.27433 0.733 0.572 2.28E−27 A96 Abcc3 Etfdh 9.29E−32 0.26388 0.811 0.706 2.31E−27 A96 Etfdh Arl4a 1.24E−31 0.27062 0.517 0.342 3.09E−27 A96 Arl4a Cpox 1.57E−31 0.32292 0.634 0.486 3.91E−27 A96 Cpox Zfp36l1 2.69E−31 0.29635 0.601 0.447 6.69E−27 A96 Zfp36l1 Dhdh1 2.78E−31 0.26256 0.734 0.615 6.90E−27 A96 Dhdh Slco1a41 5.51E−31 0.30491 0.507 0.336 1.37E−26 A96 Slco1a4 Cyp2c442 1.06E−30 0.27354 0.828 0.71 2.64E−26 A96 Cyp2c44 Ctage51 1.29E−29 0.25352 0.837 0.716 3.22E−25 A96 Ctage5 Mia31 2.42E−29 0.26045 0.81 0.659 6.02E−25 A96 Mia3 Slc25a201 3.50E−29 0.25073 0.671 0.543 8.69E−25 A96 Slc25a20 G0s22 7.31E−29 0.26556 0.525 0.35 1.81E−24 A96 G0s2 Oat2 9.25E−29 0.4904 0.653 0.478 2.30E−24 A96 Oat F5 5.35E−28 0.25658 0.858 0.754 1.33E−23 A96 F5 Cox8a3 1.48E−27 0.25185 0.737 0.626 3.67E−23 A96 Cox8a Gm49521 2.35E−27 0.25808 0.663 0.536 5.82E−23 A96 Gm4952 Pxmp4 1.07E−26 0.25548 0.687 0.556 2.65E−22 A96 Pxmp4 Ppp1r3b1 1.27E−26 0.25097 0.536 0.377 3.16E−22 A96 Ppp1r3b Fmo1 3.23E−26 0.26495 0.606 0.446 8.01E−22 A96 Fmo1 Zfp911 9.57E−26 0.27754 0.693 0.56 2.38E−21 A96 Zfp91 Apol7a1 3.42E−23 0.25176 0.559 0.42 8.50E−19 A96 Apo17a Ces1e 5.02E−22 0.2566 0.71 0.608 1.25E−17 A96 Ces1e Gadd45b 5.16E−21 0.25977 0.452 0.311 1.28E−16 A96 Gadd45b Etnppl3 6.58E−13 0.31543 0.677 0.619 1.63E−08 A96 Etnppl Mup174 0 2.01662 1 0.947 0 UT Mup17 Mup94 0 1.91449 0.976 0.594 0 UT Mup9 Mup64 0 1.88184 0.992 0.804 0 UT Mup6 Mup194 0 1.78587 1 0.916 0 UT Mup19 Mup115 0 1.72843 1 0.84 0 UT Mup11 Mup184 0 1.63857 0.997 0.838 0 UT Mup18 Mup54 0 1.34199 0.839 0.541 0 UT Mup5 Mup154 0 1.25956 0.617 0.166 0 UT Mup15 Mup164 0 1.125 0.934 0.594 0 UT Mup16 mt-Nd44 0 1.11568 0.998 0.942 0 UT mt-Nd4 mt-Co24 0 1.07773 0.629 0.157 0 UT mt-Co2 Gm137754 0 1.06127 0.761 0.306 0 UT Gm13775 mt-Co14 0 0.9219 0.999 0.977 0 UT mt-Co1 mt-Cytb3 0 0.87755 0.999 0.971 0 UT mt-Cytb Mup214 0 0.87235 0.929 0.702 0 UT Mup21 mt-Nd23 0 0.83252 0.999 0.978 0 UT mt-Nd2 Selenbp23 0 0.83043 0.937 0.751 0 UT Selenbp2 mt-Nd54 0 0.77968 0.995 0.942 0 UT mt-Nd5 mt-Nd13 0 0.75999 1 0.978 0 UT mt-Nd1 mt-Rnr22 0 0.54583 1 1 0 UT mt-Rnr2 Mup32 0 0.54248 1 0.999 0 UT Mup3 mt-Co34  1.54E−290 0.9584 0.603 0.198  3.82E−286 UT mt-Co3 Serpina1e1  1.35E−287 0.46812 0.999 0.99  3.36E−283 UT Serpina1e Akr1c62  4.68E−230 0.50466 0.971 0.92  1.16E−225 UT Akr1c6 Ankrd554  6.63E−225 1.23086 0.696 0.451  1.65E−220 UT Ankrd55 Mup43  8.62E−211 1.00077 0.898 0.716  2.14E−206 UT Mup4 mt-Rnr13  1.37E−205 0.35383 1 1  3.40E−201 UT mt-Rnr1 Fabp11  3.44E−187 0.30776 1 0.992  8.54E−183 UT Fabp1 Elovl33  5.11E−177 0.52214 0.827 0.65  1.27E−172 UT Elovl3 Gsta32  4.62E−168 0.40491 0.956 0.958  1.15E−163 UT Gsta3 Mup74  2.96E−167 0.60153 0.998 0.937  7.35E−163 UT Mup7 Nudt74  3.51E−163 0.61924 0.83 0.691  8.71E−159 UT Nudt7 Serpina1a1  1.94E−157 0.33474 0.991 0.96  4.81E−153 UT Serpina1a Uqcrq2  7.40E−157 0.41014 0.951 0.902  1.84E−152 UT Uqcrq Car32  2.61E−147 0.37625 0.974 0.956  6.47E−143 UT Car3 Ces3a2  1.36E−137 0.31735 0.967 0.93  3.38E−133 UT Ces3a Mup84  1.52E−136 0.72676 0.373 0.13  3.77E−132 UT Mup8 Adh11  1.12E−132 0.31221 0.96 0.941  2.79E−128 UT Adh1 Prdx12  2.41E−131 0.34986 0.927 0.878  5.99E−127 UT Prdx1 Gstp12  4.61E−130 0.60881 0.822 0.702  1.14E−125 UT Gstp1 Hsd3b72  3.94E−128 0.45013 0.798 0.693  9.79E−124 UT Hsd3b7 Acaa1b3  1.79E−119 0.3158 0.969 0.883  4.44E−115 UT Acaa1b Mup201  2.74E−117 0.3725 1 0.992  6.81E−113 UT Mup20 Mup133  3.18E−117 0.62497 0.546 0.351  7.90E−113 UT Mup13 Rps142  1.62E−111 0.33642 0.917 0.856  4.03E−107 UT Rsp14 Cyb52  5.75E−109 0.28445 0.983 0.972  1.43E−104 UT Cyb5 2810007J24Rik1  3.82E−107 0.28709 0.943 0.909  9.49E−103 UT 2810007J24Rik Hsd3b54  2.16E−104 0.47119 0.587 0.367  5.37E−100 UT Hsd3b5 Mup124  3.61E−104 0.37133 0.86 0.665  8.97E−100 UT Mup12 Cox4i12 2.61E−94 0.26275 0.958 0.941 6.48E−90 UT Cox4i1 Oaz11 5.51E−93 0.39443 0.75 0.651 1.37E−88 UT Oaz1 Tmem2052 1.10E−91 0.29526 0.934 0.877 2.74E−87 UT Tmem205 Serpina3c3 4.51E−84 0.42526 0.385 0.208 1.12E−79 UT Serpina3c Ugt2b11 1.86E−83 0.30063 0.871 0.817 4.62E−79 UT Ugt2b1 Rps23 3.51E−80 0.37937 0.757 0.637 8.73E−76 UT Rps2 Inmt2 1.03E−77 0.36623 0.884 0.871 2.55E−73 UT Inmt Cox6c2 1.98E−73 0.34318 0.884 0.808 4.92E−69 UT Cox6c Ndufb112 7.98E−73 0.35219 0.735 0.637 1.98E−68 UT Ndufb11 Cyp7b13 1.18E−72 0.35125 0.757 0.654 2.92E−68 UT Cyp7b1 Cyp1a22 2.21E−72 0.30346 0.794 0.621 5.49E−68 UT Cyp1a2 C8g2 9.19E−72 0.25825 0.91 0.859 2.28E−67 UT C8g Lifr3 5.26E−70 0.35319 0.694 0.608 1.31E−65 UT Lifr Hamp3 1.12E−69 0.27418 0.884 0.718 2.79E−65 UT Hamp Cfhr21 1.47E−66 0.32911 0.868 0.854 3.64E−62 UT Cfhr2 Mup143 2.61E−61 0.52442 0.616 0.469 6.49E−57 UT Mup14 Aadac2 2.88E−59 0.32428 0.86 0.849 7.15E−55 UT Aadac Keg13 4.07E−58 0.38569 0.545 0.441 1.01E−53 UT Keg1 Cyp2a52 7.24E−58 0.32734 0.555 0.388 1.80E−53 UT Cyp2a5 Chchd22 3.96E−57 0.2575 0.916 0.874 9.83E−53 UT Chchd2 Ces3b1 1.20E−56 0.28399 0.787 0.727 2.98E−52 UT Ces3b Ttc39c2 4.98E−56 0.31869 0.642 0.573 1.24E−51 UT Ttc39c Gstm32 2.30E−53 0.47361 0.414 0.269 5.70E−49 UT Gstm3 Gadd45g1 9.92E−53 0.34052 0.639 0.503 2.46E−48 UT Gadd45g Ndufa42 7.60E−52 0.26172 0.889 0.851 1.89E−47 UT Ndufa4 Cml11 7.90E−52 0.29532 0.757 0.709 1.96E−47 UT Cml1 Thrsp3 3.45E−50 0.46025 0.627 0.583 8.56E−46 UT Thrsp mt-Atp62 2.06E−48 0.41938 0.452 0.311 5.11E−44 UT mt-Atp6 Rpl321 1.00E−47 0.30384 0.757 0.688 2.49E−43 UT Rpl32 Hspe11 2.75E−44 0.30852 0.557 0.462 6.83E−40 UT Hspe1 Hsd3b31 2.62E−41 0.28285 0.605 0.519 6.51E−37 UT Hsd3b3 Serpina122 6.83E−41 0.27902 0.492 0.362 1.70E−36 UT Serpina12 Prdx41 1.19E−38 0.2905 0.607 0.55 2.95E−34 UT Prdx4 Mup24 3.60E−37 0.4469 0.392 0.285 8.95E−33 UT Mup2 Cox7a22 2.72E−36 0.2511 0.784 0.722 6.76E−32 UT Cox7a2 Cyp2b102 2.41E−35 0.50278 0.542 0.493 5.98E−31 UT Cyp2b10 Ndufs62 3.36E−32 0.27205 0.724 0.678 8.33E−28 UT Ndufs6 Ndufb41 1.61E−29 0.25309 0.49 0.409 3.99E−25 UT Ndufb4 Rpl36al1 8.10E−27 0.27021 0.551 0.495 2.01E−22 UT Rpl36al Mup116 1.57E−24 0.47001 0.583 0.522 3.91E−20 UT Mup1 Rps152 4.98E−19 0.27219 0.528 0.49 1.24E−14 UT Rps15 Ubb 5.31E−19 0.26415 0.45 0.394 1.32E−14 UT Ubb Ftl1 2.27E−15 0.30999 0.409 0.367 5.64E−11 UT Ftl1

Clear pericentral to periportal gradients were observed across all clusters except 6 hours post-APAP, due to the pericentral-specific injury in this model. Interestingly, a return of pericentral, Cyp2e1-expressing hepatocytes was observed by 24 hrs, which is earlier than peak regeneration time of 36 to 48 hours, suggesting possible gene expression reprogramming within existing surviving hepatocytes. Tables 2-7 provide differentially expressed genes between particular time points and untreated cells, time points A6, A24, A48A96, PHX3 FC.1, PHX3 FC.2 and PHX3 FC.15, respectively.

TABLE 2 Differentially expressed genes between time point A6 and untreated (UT). ID p_val avg_logFC pct.1 pct.2 p_val_adj Mt1 0 2.387707773 0.981 0.556 0 Mt2 0 2.06273693 0.938 0.365 0 Gclc 0 1.902837282 0.962 0.718 0 Srxn1 0 1.878352012 0.821 0.189 0 Plin2 0 1.461295758 0.943 0.714 0 Fabp1 0 −1.016174848 0.971 1 0 Akr1c6 0 −1.586259995 0.675 0.971 0 Mup17 0 −2.354358557 0.871 1 0 Mup19 0 −2.396345291 0.759 1 0 Mup11 0 −3.213953203 0.511 1 0 Gpx1 4.15457073465707e−311 −0.768556331 0.969 0.999  1.03E−306 Txnrd1 1.45669736974939e−310 1.443578942 0.838 0.441  3.62E−306 Adh1 0.00E+00 −1.255028206 0.74 0.96  2.34E−304 Apoc1  1.03E−305 −0.871282735 0.962 0.999  2.55E−301 Mgst1  6.50E−299 −1.060154854 0.938 0.997  1.61E−294 Gm26924  3.46E−287 1.16085221 1 1  8.60E−283 Krt18  5.85E−282 1.257881489 0.864 0.617  1.45E−277 Actb  9.88E−280 1.059835055 0.979 0.886  2.45E−275 Mup3  9.44E−277 −0.703483173 1 1  2.34E−272 Krt8  3.88E−263 1.195874806 0.826 0.578  9.64E−259 Cyp2e1  1.17E−251 −2.318570161 0.162 0.911  2.90E−247 Apoc4  1.91E−232 −1.002265767 0.831 0.98  4.73E−228 Mup16  1.87E−230 −1.602085539 0.334 0.934  4.64E−226 Serpina3m  5.23E−230 0.967441963 0.85 0.722  1.30E−225 Mup9  9.88E−226 −2.004163996 0.489 0.976  2.45E−221 Hmox1  2.37E−215 1.347585217 0.558 0.016  5.89E−211 Tnfrsf12a  5.66E−215 1.117506296 0.623 0.052  1.40E−210 Apoc3  3.15E−214 −0.768781074 0.869 0.993  7.83E−210 Apoa2  1.12E−201 −0.542784959 0.993 1  2.78E−197 Apoa4  2.86E−200 1.367998503 0.721 0.339  7.09E−196 Gm15564  3.29E−198 1.443066465 0.983 0.956  8.17E−194 Rgn  8.29E−196 −1.573093006 0.243 0.874  2.06E−191 Hbb-bs  2.32E−195 2.862044849 0.537 0.018  5.76E−191 Mup18  4.75E−195 −1.627956781 0.728 0.997  1.18E−190 Lars2  1.29E−190 1.391744455 1 0.994  3.20E−186 Chka  1.19E−189 1.375010255 0.716 0.231  2.97E−185 Cdkn1a  2.01E−187 1.2152557 0.702 0.195  4.98E−183 Il1r1  4.05E−186 1.244999819 0.683 0.167  1.01E−181 Car3  1.31E−184 −1.036093133 0.854 0.974  3.26E−180 Myh9  2.05E−183 1.160233135 0.718 0.318  5.08E−179 Igfbp1  1.50E−181 1.058689301 0.792 0.717  3.71E−177 Nudt7  5.65E−175 −1.564266936 0.279 0.83  1.40E−170 Slco1b2  3.15E−172 −1.087378176 0.678 0.951  7.83E−168 Mat1a  5.22E−167 0.790765268 0.986 0.966  1.30E−162 Hnf4a  6.47E−166 0.879108718 0.835 0.743  1.61E−161 Mup6  1.14E−164 −1.871852037 0.706 0.992  2.82E−160 Cyp4a14  1.96E−161 1.122498795 0.776 0.431  4.86E−157 Fga  3.87E−160 0.69335023 0.986 0.997  9.60E−156 Slc39a14  4.45E−159 1.012749203 0.678 0.343  1.10E−154 S100a9  1.09E−157 1.342849617 0.399 0.004  2.70E−153 Lrrc58  6.48E−157 1.001096085 0.711 0.359  1.61E−152 Cyp2c29  1.48E−156 −1.149629979 0.418 0.93  3.68E−152 Mup12  8.02E−156 −1.269973728 0.32 0.86  1.99E−151 Ppl  2.58E−155 0.879840886 0.47 0.022  6.41E−151 2810007J24Rik  4.24E−152 −0.914301122 0.675 0.943  1.05E−147 1100001G20Rik  3.93E−151 −0.851607217 0.862 0.982  9.75E−147 Selenbp2  5.10E−151 −1.009165718 0.609 0.937  1.27E−146 Serpina3n  1.42E−146 0.848313239 0.747 0.574  3.52E−142 Ttr  1.21E−145 −0.530625643 0.993 1  3.01E−141 S100a8  4.44E−145 1.127879209 0.353 0.001  1.10E−140 Slc16a6  3.23E−141 0.911357108 0.47 0.054  8.03E−137 Mrap  8.89E−139 0.884099926 0.606 0.272  2.21E−134 Fgb  1.34E−136 0.646934246 0.995 1  3.33E−132 Uqcrq  1.27E−135 −0.88665513 0.721 0.951  3.15E−131 Pck1  1.82E−134 −0.652190949 0.814 0.987  4.52E−130 Fam134b  1.16E−133 0.893562894 0.678 0.405  2.87E−129 Rnase4  3.04E−133 −1.049196753 0.563 0.921  7.54E−129 mt-Nd4  3.12E−131 −0.638848134 0.964 0.998  7.74E−127 Dbi  6.97E−127 −0.716365271 0.819 0.971  1.73E−122 Fgg  2.32E−125 0.615329068 0.986 0.991  5.76E−121 Hilpda  4.59E−125 0.778625914 0.403 0.024  1.14E−120 Hsd3b7  1.37E−123 −1.0059958 0.387 0.798  3.41E−119 Cyb5  2.11E−122 −0.71018958 0.916 0.983  5.23E−118 Hsd3b5  1.42E−120 −1.069520224 0.062 0.587  3.51E−116 Gsta3  1.52E−120 −0.806290466 0.885 0.956  3.76E−116 Oat  2.95E−120 −1.224853019 0.05 0.611  7.33E−116 Trp53inp1  3.61E−120 1.008414088 0.637 0.308  8.96E−116 Cyp2a5  1.79E−119 −1.498910166 0.019 0.555  4.44E−115 Hamp  6.15E−119 −1.02112368 0.422 0.884  1.53E−114 Apoe  1.31E−118 −0.368966531 1 1  3.25E−114 Psen2  1.68E−118 −0.947373772 0.384 0.774  4.17E−114 Tmem205  3.80E−116 −0.774742732 0.695 0.934  9.43E−112 Mup15  1.54E−114 −1.316464146 0.076 0.617  3.83E−110 Cyp3a11  2.00E−114 −0.423130745 0.964 1  4.96E−110 Sqstm1  1.89E−113 0.743150456 0.859 0.805  4.70E−109 Acaa1b  2.10E−113 −0.732823459 0.752 0.969  5.21E−109 Mup7  6.91E−111 −0.941370494 0.831 0.998  1.72E−106 Cyp8b1  2.65E−108 −0.889229825 0.282 0.745  6.59E−104 Gm13775  5.84E−107 −1.065618856 0.284 0.761  1.45E−102 Bcl2l1  5.29E−106 0.775118224 0.501 0.122  1.31E−101 Insig2  9.46E−104 0.669991504 0.854 0.81 2.35E−99 Tubb2a  1.34E−101 0.749433744 0.618 0.431 3.32E−97 Sdc4  1.77E−100 0.619597869 0.909 0.867 4.40E−96 Iigp1  2.96E−100 0.768753667 0.78 0.759 7.35E−96 Klf6 1.89E−98 0.732407935 0.382 0.034 4.69E−94 Eif1a 2.08E−98 0.795281298 0.599 0.289 5.16E−94 Rps27l 3.09E−97 −0.865927484 0.484 0.849 7.67E−93 Mup21 4.96E−97 −0.827249928 0.58 0.929 1.23E−92 Cyp2d9 5.06E−97 −0.640698605 0.747 0.959 1.26E−92 Ccl6 7.03E−97 0.78914235 0.274 0.006 1.75E−92 Ugt2b5 7.03E−97 −0.603351248 0.847 0.959 1.75E−92 Adck3 1.08E−96 −0.87611538 0.363 0.764 2.67E−92 Tubb6 2.37E−96 0.576687679 0.368 0.03 5.89E−92 G6pc 4.32E−96 −0.960058274 0.313 0.752 1.07E−91 Cltc 7.08E−96 0.784985399 0.661 0.414 1.76E−91 Hbb-bt 2.95E−95 1.430134393 0.246 0.002 7.33E−91 Srgn 2.10E−94 0.934067453 0.284 0.01 5.22E−90 Sec1412 2.77E−94 −0.789737513 0.484 0.856 6.88E−90 Cyp1a2 1.21E−93 −0.993935836 0.353 0.794 3.00E−89 mt-Nd1 2.49E−93 −0.388336084 0.983 1 6.19E−89 Epas1 2.59E−93 0.775763153 0.604 0.297 6.43E−89 Ets2 3.90E−93 0.695623802 0.415 0.056 9.69E−89 Ttc36 8.91E−93 −0.660645659 0.768 0.95 2.21E−88 Ugt2b1 2.20E−92 −0.776816931 0.561 0.871 5.46E−88 Cox6c 1.10E−91 −0.844280539 0.558 0.884 2.73E−87 Btg2 1.58E−91 0.832086378 0.549 0.241 3.93E−87 Xbp1 5.43E−91 0.603165814 0.692 0.57 1.35E−86 Hspb8 7.33E−90 0.633933124 0.709 0.597 1.82E−85 Sod1 8.95E−90 −0.439319795 0.931 0.983 2.22E−85 Cers6 1.45E−89 0.532818648 0.332 0.022 3.61E−85 2010003K11Rik 8.77E−89 0.588354735 0.396 0.046 2.18E−84 Hgd 9.82E−89 −0.758572265 0.511 0.861 2.44E−84 Urah 5.16E−88 −0.764109132 0.525 0.852 1.28E−83 H3f3b 2.47E−86 0.702914634 0.613 0.419 6.14E−82 Picalm 2.64E−86 0.754529703 0.647 0.376 6.55E−82 Bach1 1.42E−85 0.832333098 0.461 0.151 3.52E−81 Eif5 1.50E−85 0.576301866 0.816 0.74 3.73E−81 Ugdh 2.38E−84 0.633076584 0.721 0.604 5.92E−80 Aldh3a2 2.55E−84 −0.834229334 0.064 0.529 6.32E−80 Ddx3x 2.89E−84 0.656890035 0.692 0.513 7.19E−80 Gjb2 4.51E−84 0.60822545 0.678 0.572 1.12E−79 Rcan1 1.03E−82 0.707283787 0.425 0.085 2.56E−78 Nid1 1.05E−82 0.342599117 0.229 0.003 2.60E−78 Hsd3b3 1.20E−82 −0.779501123 0.174 0.605 2.98E−78 Keg1 2.46E−82 −0.824548137 0.134 0.545 6.12E−78 Cxadr 3.65E−82 0.698450944 0.606 0.345 9.07E−78 Hsd17b13 3.30E−80 0.680828119 0.864 0.74 8.20E−76 Il1b 3.56E−80 0.742893545 0.236 0.005 8.84E−76 Ubc 8.91E−80 −0.661839716 0.573 0.872 2.21E−75 Stat3 1.03E−79 0.715400235 0.604 0.318 2.55E−75 Asl 1.49E−79 0.558638879 0.826 0.787 3.70E−75 Ces3a 4.62E−79 −0.52533635 0.831 0.967 1.15E−74 Psat1 4.90E−79 0.301248562 0.229 0.004 1.22E−74 C8g 5.15E−79 −0.654510262 0.673 0.91 1.28E−74 Gulo 5.44E−79 −0.801665727 0.076 0.497 1.35E−74 Itih3 2.22E−78 0.546240791 0.907 0.89 5.51E−74 Abca1 4.43E−78 0.724477701 0.604 0.377 1.10E−73 Pon1 8.86E−78 −0.685751275 0.685 0.906 2.20E−73 Scp2 2.00E−77 −0.519124916 0.866 0.986 4.98E−73 Clec4f 1.18E−76 1.108180782 0.339 0.043 2.94E−72 Eif4g2 6.68E−76 0.559692663 0.757 0.678 1.66E−71 Oaf 1.37E−75 −0.7328674 0.437 0.794 3.40E−71 Slc22a1 8.96E−75 −0.797941816 0.36 0.747 2.23E−70 n-R5-8s1 1.47E−74 0.766100662 0.308 0.031 3.65E−70 Rell1 1.19E−73 0.591181865 0.375 0.063 2.97E−69 Hpd 1.20E−73 −0.518180386 0.883 0.976 2.98E−69 Gpt2 1.39E−73 0.539114072 0.764 0.725 3.45E−69 Sat1 1.97E−73 0.68869896 0.47 0.167 4.89E−69 Ddx21 2.38E−73 0.73138069 0.535 0.22 5.90E−69 Mfsd2a 6.35E−73 0.666142747 0.465 0.148 1.58E−68 Cox4i1 2.09E−72 −0.515989169 0.869 0.958 5.19E−68 Pcbd1 2.64E−72 −0.687761883 0.535 0.837 6.57E−68 Mup5 4.12E−72 −1.23728834 0.475 0.839 1.02E−67 Cyp2c37 5.90E−72 −0.886903784 0.177 0.608 1.47E−67 Eef2 5.96E−72 0.525855561 0.9 0.873 1.48E−67 Ugt2b36 6.92E−72 −0.583431487 0.745 0.93 1.72E−67 Mbl1 1.03E−71 −0.713006005 0.382 0.749 2.56E−67 Ctsl 1.19E−71 0.530101805 0.878 0.857 2.95E−67 mt-Co2 1.33E−71 −1.105332856 0.2 0.629 3.31E−67 Hacl1 1.55E−71 −0.706897734 0.489 0.797 3.86E−67 D10Wsu102e 1.62E−71 0.58780186 0.37 0.063 4.02E−67 Ankrd55 1.94E−71 −1.250834631 0.372 0.696 4.83E−67 Nop58 2.01E−71 0.663449653 0.492 0.162 4.99E−67 Hint1 2.70E−71 −0.673880575 0.57 0.858 6.70E−67 Retsat 4.73E−71 0.491096059 0.845 0.83 1.18E−66 Hagh 4.00E−70 −0.674009711 0.573 0.858 9.93E−66 Rora 6.90E−70 0.644354953 0.549 0.341 1.71E−65 Ndufa4 1.71E−69 −0.683126695 0.656 0.889 4.24E−65 Upp2 2.20E−67 −0.69025963 0.274 0.673 5.46E−63 Lpin2 3.08E−67 0.686687426 0.745 0.597 7.64E−63 Wbp1l 1.00E−66 0.553507326 0.697 0.606 2.49E−62 Tnfrsf1a 2.12E−66 0.599573483 0.508 0.244 5.27E−62 Itih2 6.50E−65 0.501091194 0.893 0.884 1.61E−60 Inmt 9.14E−65 −0.731016404 0.709 0.884 2.27E−60 Apob 1.91E−64 0.580156235 0.99 0.989 4.73E−60 Dusp5 2.61E−64 0.296374788 0.196 0.005 6.47E−60 Gm24601 3.58E−64 0.46836359 0.241 0.015 8.89E−60 Aldh8a1 3.87E−64 −0.683676902 0.418 0.758 9.60E−60 Lpgat1 4.83E−64 0.595219291 0.618 0.502 1.20E−59 Hba-a1 4.96E−64 0.734957385 0.165 0.001 1.23E−59 Glyat 1.28E−63 −0.647687911 0.468 0.798 3.18E−59 Lect2 4.58E−63 −0.626967771 0.045 0.414 1.14E−58 Plscr1 4.87E−63 0.444489505 0.329 0.047 1.21E−58 Cidec 8.20E−63 0.299384206 0.253 0.019 2.04E−58 Uqcr11 1.20E−62 −0.603079991 0.606 0.879 2.97E−58 Tmsb4x 1.25E−62 0.780616209 0.332 0.057 3.10E−58 Hebp1 2.37E−62 −0.635432267 0.43 0.75 5.88E−58 Hes6 2.98E−62 −0.561302344 0.076 0.42 7.39E−58 Atp5e 5.29E−62 −0.650247857 0.506 0.832 1.31E−57 mmu-mir-6240 8.16E−62 1.101237189 0.413 0.115 2.03E−57 Efhd2 2.27E−61 0.583831769 0.468 0.148 5.63E−57 Msrb1 2.71E−61 −0.59903268 0.558 0.838 6.72E−57 8430408G22Rik 2.51E−60 −0.50210224 0.041 0.392 6.22E−56 Tlcd2 4.44E−60 −0.594498821 0.186 0.536 1.10E−55 Serpina1a 5.95E−60 −0.378457074 0.914 0.991 1.48E−55 Leap2 1.65E−59 −0.671300937 0.26 0.632 4.10E−55 Rdh7 1.97E−59 −0.418625957 0.862 0.969 4.88E−55 Gcnt2 2.40E−59 0.537509676 0.372 0.082 5.96E−55 Uox 2.52E−59 −0.553115511 0.905 0.965 6.26E−55 Acss2 9.19E−59 −0.620071374 0.248 0.574 2.28E−54 Prdx1 1.04E−58 −0.529229113 0.742 0.927 2.58E−54 Lrg1 1.21E−58 0.490792829 0.783 0.736 2.99E−54 Mup13 1.81E−58 −0.77574306 0.205 0.546 4.49E−54 Cox7b 4.10E−58 −0.642240776 0.632 0.878 1.02E−53 Myo1e 4.83E−58 0.614341001 0.475 0.182 1.20E−53 Mmp8 7.38E−58 0.359005863 0.136 0 1.83E−53 Ttc39c 7.39E−58 −0.636274928 0.325 0.642 1.84E−53 Gn13 7.72E−58 0.575970422 0.501 0.204 1.92E−53 B4galt5 1.31E−57 0.476306558 0.332 0.07 3.26E−53 Mup4 1.88E−57 −0.99530818 0.621 0.898 4.67E−53 Ndufa6 2.60E−57 −0.613649978 0.506 0.798 6.47E−53 Ang 4.44E−57 −0.662883759 0.315 0.687 1.10E−52 Alb 8.54E−57 0.420298986 1 1 2.12E−52 Cyp7b1 8.74E−57 −0.65802273 0.42 0.757 2.17E−52 C230081A13Rik 8.95E−57 0.426976229 0.279 0.035 2.22E−52 Fn1 1.95E−56 0.521230804 0.847 0.821 4.85E−52 Cox7a2 2.11E−56 −0.650338386 0.456 0.784 5.23E−52 Man2a1 2.93E−56 0.497115325 0.671 0.583 7.27E−52 Cyp2c50 3.04E−56 −0.661823297 0.616 0.888 7.54E−52 Jmjd1c 4.80E−56 0.636619821 0.47 0.178 1.19E−51 Apol7a 6.85E−56 −0.492294435 0.072 0.382 1.70E−51 Jak1 6.86E−56 0.603850485 0.554 0.342 1.70E−51 Haao 7.05E−56 −0.591181029 0.621 0.861 1.75E−51 St3gal5 2.58E−55 0.607639775 0.706 0.49 6.40E−51 Ctss 5.17E−55 0.764167083 0.212 0.019 1.28E−50 Ywhag 1.12E−54 0.58241474 0.518 0.308 2.78E−50 Rarres2 1.90E−54 −0.552194576 0.678 0.905 4.73E−50 Mthfd2 2.03E−54 0.262448025 0.205 0.012 5.03E−50 St3gal1 3.04E−54 0.528739882 0.473 0.221 7.55E−50 Fdx1 3.17E−54 −0.623439092 0.305 0.625 7.87E−50 Chchd2 3.70E−54 −0.552503492 0.718 0.916 9.20E−50 Lactb2 4.06E−54 −0.596505052 0.47 0.751 1.01E−49 Phlda1 4.10E−54 0.549174347 0.494 0.356 1.02E−49 Cd14 1.17E−53 0.362089625 0.153 0.003 2.91E−49 2-Mar 1.24E−53 −0.55994977 0.611 0.865 3.08E−49 Aass 1.93E−53 0.477517138 0.747 0.716 4.80E−49 Clqb 2.33E−53 0.681679654 0.234 0.024 5.78E−49 Hsd17b2 3.46E−53 −0.595878526 0.391 0.711 8.60E−49 Cml1 1.92E−52 −0.61424052 0.475 0.757 4.76E−48 Adh6-ps1 6.36E−52 −0.418504072 0.017 0.313 1.58E−47 Tyrobp 6.73E−52 0.466551501 0.189 0.011 1.67E−47 Retnlg 8.59E−52 0.375148336 0.129 0 2.13E−47 Arhgef12 1.06E−51 0.590764816 0.578 0.408 2.62E−47 Pah 1.69E−51 −0.52207695 0.687 0.891 4.20E−47 Rock2 3.56E−51 0.594094466 0.425 0.131 8.83E−47 Tra2a 3.81E−51 0.712328169 0.337 0.1 9.46E−47 Creb3l2 4.81E−51 0.427180051 0.329 0.068 1.19E−46 Etf1 5.70E−51 0.559444816 0.606 0.409 1.41E−46 Ddx5 1.56E−50 0.522944475 0.685 0.515 3.88E−46 Cd302 1.61E−50 −0.549925078 0.649 0.86 3.99E−46 Arl4d 1.86E−50 −0.507228317 0.112 0.437 4.61E−46 Grn 3.15E−50 0.540768685 0.582 0.396 7.83E−46 Agpat9 3.32E−50 0.327040595 0.277 0.038 8.25E−46 Adh4 3.58E−50 −0.526868306 0.165 0.521 8.89E−46 Lifr 6.21E−50 −0.626180925 0.389 0.694 1.54E−45 Hba-a2 7.25E−50 0.553546734 0.131 0.001 1.80E−45 Tiparp 1.75E−49 0.545567123 0.346 0.087 4.34E−45 Gamt 2.68E−49 −0.560282685 0.277 0.591 6.66E−45 C3 5.98E−49 0.44276078 0.993 0.99 1.49E−44 Fxyd5 7.03E−49 0.274279595 0.138 0.002 1.74E−44 Cd5l 9.18E−49 0.693485826 0.21 0.026 2.28E−44 Fkbp5 1.09E−48 0.516128063 0.415 0.117 2.70E−44 Gsta1 1.15E−48 0.407606856 0.32 0.062 2.85E−44 Atp2a2 1.30E−48 0.494962728 0.616 0.495 3.22E−44 Ppib 1.44E−48 −0.589699514 0.463 0.767 3.58E−44 Ndufb2 3.05E−48 −0.577154458 0.301 0.629 7.57E−44 1-Mar 3.12E−48 −0.477762617 0.644 0.885 7.75E−44 Mcm10 3.33E−48 −0.487427572 0.079 0.386 8.27E−44 Dusp6 3.94E−48 0.59164596 0.482 0.261 9.78E−44 Fabp2 5.11E−48 −0.615569339 0.315 0.622 1.27E−43 Stk40 8.11E−48 0.536418312 0.382 0.121 2.01E−43 Ddt 9.71E−48 −0.522221147 0.539 0.829 2.41E−43 Hif1a 1.06E−47 0.516911277 0.427 0.166 2.63E−43 Ppm1k 1.93E−47 −0.558394496 0.15 0.45 4.79E−43 Akr1c20 2.15E−47 −0.554152364 0.248 0.564 5.34E−43 Csf1r 2.32E−47 0.704458586 0.184 0.015 5.76E−43 Aadac 2.83E−47 −0.619958028 0.673 0.86 7.04E−43 Saa4 3.63E−47 −0.571021905 0.437 0.749 9.02E−43 Pemt 5.32E−47 −0.551184095 0.492 0.78 1.32E−42 Atp5h 5.87E−47 −0.6398091 0.377 0.682 1.46E−42 Slc25a47 7.64E−47 0.428932953 0.869 0.927 1.90E−42 Ranbp2 8.46E−47 0.598499679 0.566 0.338 2.10E−42 Aldh1a1 1.08E−46 −0.478797447 0.862 0.956 2.68E−42 Ptprc 1.10E−46 0.416505491 0.153 0.006 2.72E−42 Lyz2 2.06E−46 0.732183369 0.234 0.032 5.12E−42 Abhd2 2.14E−46 0.484366625 0.37 0.105 5.33E−42 1700017B05Rik 2.19E−46 0.330656885 0.255 0.037 5.43E−42 Ndufb9 2.30E−46 −0.503828812 0.661 0.888 5.71E−42 Pla2g7 2.76E−46 0.282344956 0.119 0.001 6.85E−42 Adamts1 3.06E−46 0.282556845 0.2 0.018 7.60E−42 Malat1 3.47E−46 0.920628097 0.871 0.78 8.61E−42 Cox6a1 3.93E−46 −0.48722865 0.675 0.887 9.76E−42 Gstz1 5.09E−46 −0.464086834 0.73 0.905 1.26E−41 1600014C10Rik 7.24E−46 −0.498182953 0.167 0.462 1.80E−41 Aff4 8.92E−46 0.616309327 0.537 0.337 2.21E−41 Clec4d 1.07E−45 0.26359638 0.107 0 2.66E−41 Egr1 1.20E−45 0.584558888 0.589 0.447 2.98E−41 Atp5j2 1.26E−45 −0.51308051 0.606 0.852 3.12E−41 Eaf1 1.85E−45 0.521796522 0.427 0.168 4.59E−41 Qdpr 2.35E−45 −0.52357376 0.606 0.814 5.84E−41 Il1r2 2.51E−45 0.323447978 0.117 0.001 6.22E−41 Tars 3.11E−45 0.492059498 0.666 0.539 7.73E−41 Mcl1 5.48E−45 0.570934356 0.573 0.371 1.36E−40 Serpina1d 5.92E−45 −0.289011223 0.926 0.988 1.47E−40 Ncl 1.05E−44 0.48450982 0.69 0.567 2.60E−40 Gm4952 1.47E−44 −0.49867829 0.198 0.533 3.64E−40 Gchfr 2.75E−44 −0.554783473 0.489 0.768 6.83E−40 Ndufa7 2.91E−44 −0.555912274 0.406 0.718 7.23E−40 Dio1 3.74E−44 −0.545283744 0.253 0.542 9.29E−40 Cyp7a1 4.21E−44 −0.431201844 0.01 0.259 1.04E−39 Mpc2 5.18E−44 −0.482839417 0.599 0.857 1.29E−39 Son 6.25E−44 0.542911509 0.601 0.358 1.55E−39 Thrsp 7.87E−44 −0.724961807 0.384 0.627 1.95E−39 Nit2 9.38E−44 −0.485940613 0.301 0.577 2.33E−39 Btg1 1.09E−43 0.458007046 0.356 0.101 2.70E−39 Epb4.1 1.81E−43 0.562789274 0.537 0.304 4.50E−39 Spred1 2.85E−43 0.388422711 0.308 0.069 7.08E−39 Tm4sf4 3.17E−43 0.512552747 0.484 0.256 7.87E−39 Vcam1 4.97E−43 0.457401491 0.134 0.004 1.23E−38 Atp5f1 6.07E−43 −0.517061165 0.69 0.869 1.51E−38 Cldn14 6.28E−43 0.364540783 0.32 0.076 1.56E−38 Adh5 7.79E−43 −0.491433382 0.649 0.854 1.94E−38 Cyp2c70 8.22E−43 −0.551134023 0.587 0.834 2.04E−38 Gm26917 1.07E−42 0.60120474 0.382 0.181 2.66E−38 Cd163 2.23E−42 0.440845529 0.146 0.008 5.54E−38 Tmem87b 3.21E−42 0.434399269 0.351 0.096 7.98E−38 Csad 4.42E−42 −0.559786018 0.473 0.744 1.10E−37 Elovl3 5.34E−42 −0.506724135 0.568 0.827 1.33E−37 Cyp4a10 6.21E−42 0.456645767 0.687 0.657 1.54E−37 Mup8 8.20E−42 −0.752577709 0.098 0.373 2.04E−37 Ctsb 8.90E−42 0.521310448 0.804 0.781 2.21E−37 Iqgap1 9.52E−42 0.45544473 0.162 0.012 2.36E−37 Herpud1 1.01E−41 −0.497586072 0.535 0.803 2.51E−37 Rplp1 1.47E−41 −0.504662964 0.449 0.757 3.64E−37 Ndufb6 1.70E−41 −0.507682563 0.475 0.759 4.21E−37 Khk 2.56E−41 −0.491453217 0.702 0.863 6.36E−37 Heatr1 3.13E−41 0.406005371 0.291 0.062 7.78E−37 Dhrs3 3.16E−41 −0.467621234 0.198 0.465 7.85E−37 Crp 3.31E−41 −0.506869364 0.477 0.756 8.23E−37 Plek 3.32E−41 0.308857869 0.11 0.001 8.24E−37 Ebpl 8.84E−41 −0.450334658 0.196 0.451 2.20E−36 Trf 9.22E−41 −0.261883505 0.988 1 2.29E−36 Akr1c14 1.02E−40 −0.518570798 0.413 0.707 2.54E−36 Cox5b 4.90E−40 −0.498783616 0.425 0.726 1.22E−35 Ndufb11 5.25E−40 −0.509671057 0.461 0.735 1.30E−35 Dusp16 5.69E−40 0.46051738 0.372 0.149 1.41E−35 Rnf144a 5.85E−40 0.313046134 0.177 0.015 1.45E−35 Sult1a1 6.44E−40 0.318989978 0.685 0.707 1.60E−35 Kctd3 6.81E−40 0.260833465 0.239 0.036 1.69E−35 Serpina1e 7.25E−40 −0.268413792 0.99 0.999 1.80E−35 Lcn2 1.07E−39 0.412194792 0.301 0.07 2.67E−35 Wfdc17 1.33E−39 0.486653465 0.177 0.018 3.31E−35 Hibadh 2.75E−39 −0.499409672 0.542 0.791 6.84E−35 Rpl32 4.14E−39 −0.532218378 0.501 0.757 1.03E−34 Lyst 4.87E−39 0.409280587 0.31 0.073 1.21E−34 Errfi1 5.94E−39 0.393680047 0.943 0.911 1.47E−34 Apoh 6.38E−39 −0.262314298 0.924 0.986 1.58E−34 Tmem256 7.18E−39 −0.518510202 0.375 0.667 1.78E−34 Atp5j 8.66E−39 −0.48373528 0.492 0.757 2.15E−34 Chic2 1.01E−38 0.419790279 0.37 0.128 2.51E−34 Fxyd1 1.67E−38 −0.479908398 0.432 0.721 4.15E−34 Dot1l 2.53E−38 0.397036294 0.282 0.066 6.29E−34 Blvrb 2.64E−38 −0.545112721 0.286 0.564 6.56E−34 Atp1a1 3.98E−38 0.419079339 0.53 0.457 9.89E−34 Sord 5.54E−38 −0.383628337 0.754 0.931 1.38E−33 Ssr4 6.38E−38 −0.507577243 0.413 0.687 1.58E−33 Selenbp1 6.88E−38 −0.493707332 0.401 0.699 1.71E−33 Tbc1d15 9.36E−38 0.488646353 0.461 0.244 2.32E−33 Ndufs6 1.21E−37 −0.537929827 0.482 0.724 3.01E−33 Fndc3b 1.22E−37 0.409645989 0.315 0.096 3.04E−33 C1qc 1.37E−37 0.586092716 0.172 0.018 3.40E−33 Tsr1 1.46E−37 0.360287403 0.341 0.097 3.63E−33 Slc10a2 1.62E−37 0.299006165 0.255 0.05 4.03E−33 Gnmt 2.11E−37 −0.33340449 0.962 0.988 5.24E−33 Lonp2 2.72E−37 −0.467365882 0.561 0.814 6.76E−33 Pabpc1 3.30E−37 0.410051805 0.697 0.592 8.20E−33 Rsp14 3.48E−37 −0.402093042 0.745 0.917 8.64E−33 Chchd10 3.74E−37 −0.40191686 0.802 0.944 9.28E−33 C1qa 4.78E−37 0.514846404 0.174 0.02 1.19E−32 Dgkd 5.13E−37 0.370844881 0.282 0.069 1.27E−32 Ppp1r3b 7.31E−37 −0.402657788 0.098 0.38 1.82E−32 Atp5k 1.05E−36 −0.47725773 0.368 0.678 2.61E−32 Fam107b 1.11E−36 0.463320341 0.449 0.238 2.75E−32 Rarres1 1.54E−36 −0.455632451 0.155 0.42 3.84E−32 Cd74 1.65E−36 0.453937562 0.155 0.012 4.09E−32 Cald1 1.80E−36 0.373703655 0.766 0.749 4.47E−32 Cyp2c67 1.95E−36 −0.463488581 0.126 0.418 4.85E−32 Klf15 2.28E−36 −0.451831953 0.208 0.473 5.65E−32 Kif5b 2.63E−36 0.50116686 0.494 0.303 6.52E−32 Reep3 6.36E−36 0.409014614 0.535 0.422 1.58E−31 Rgs2 8.14E−36 0.395729601 0.138 0.01 2.02E−31 Rad54l2 1.08E−35 0.388705156 0.325 0.092 2.69E−31 Ndufb4 1.39E−35 −0.453693039 0.212 0.49 3.46E−31 Hic2 1.39E−35 0.289767391 0.15 0.012 3.46E−31 Laptm5 1.89E−35 0.338180771 0.124 0.006 4.69E−31 Tjp2 2.38E−35 0.411461753 0.332 0.114 5.91E−31 Ndufa13 2.55E−35 −0.43876131 0.549 0.802 6.33E−31 Tmed5 2.73E−35 0.401633325 0.594 0.492 6.77E−31 Lgmn 2.88E−35 0.484586871 0.246 0.059 7.14E−31 Mettl7b 2.95E−35 −0.452656656 0.647 0.869 7.34E−31 Ptpn1 3.04E−35 0.41633121 0.353 0.107 7.55E−31 Cd44 4.20E−35 0.303745221 0.115 0.004 1.04E−30 H2-Ab1 4.30E−35 0.460956687 0.158 0.015 1.07E−30 Cd97 4.52E−35 0.345774315 0.115 0.004 1.12E−30 1500017E21Rik 5.38E−35 −0.460997215 0.217 0.476 1.34E−30 Cyp3a25 6.56E−35 −0.386094858 0.728 0.919 1.63E−30 Nolc1 8.57E−35 0.47222269 0.363 0.134 2.13E−30 Hpgd 9.04E−35 −0.387752401 0.115 0.394 2.25E−30 Nars 1.16E−34 0.437769953 0.606 0.471 2.88E−30 Dst 1.47E−34 0.510971252 0.43 0.206 3.66E−30 Mdn1 1.76E−34 0.317989246 0.251 0.051 4.37E−30 Mbnl1 2.34E−34 0.451258107 0.492 0.297 5.81E−30 Comt 2.52E−34 −0.368377448 0.776 0.931 6.25E−30 Agmat 2.99E−34 −0.471832829 0.339 0.604 7.44E−30 Stard10 3.47E−34 −0.338316568 0.876 0.967 8.61E−30 Mat2a 4.43E−34 0.482570924 0.487 0.279 1.10E−29 Plec 4.56E−34 0.467512335 0.422 0.186 1.13E−29 Mrp114 5.17E−34 −0.459040925 0.258 0.523 1.28E−29 Gm24187 5.89E−34 0.431940663 0.2 0.032 1.46E−29 Hspe1 6.06E−34 −0.480734946 0.294 0.557 1.50E−29 Gtpbp4 6.17E−34 0.482239467 0.477 0.262 1.53E−29 Etfb 1.03E−33 −0.365490277 0.802 0.94 2.57E−29 Tsku 1.17E−33 0.36762763 0.327 0.095 2.90E−29 Brd2 1.82E−33 0.571515166 0.542 0.408 4.52E−29 Tacc2 2.29E−33 0.329332932 0.289 0.071 5.70E−29 Uqcr10 2.44E−33 −0.45190185 0.561 0.8 6.05E−29 Ell2 2.61E−33 0.417241283 0.535 0.416 6.49E−29 Hpx 3.10E−33 −0.303288229 0.988 0.997 7.71E−29 H6pd 3.17E−33 0.343718187 0.623 0.595 7.88E−29 Tsc22d2 3.40E−33 0.391059638 0.353 0.124 8.44E−29 Rpl36al 3.73E−33 −0.475541391 0.284 0.551 9.26E−29 Sdad1 4.01E−33 0.312421192 0.289 0.072 9.96E−29 Itgb2 6.11E−33 0.272302012 0.105 0.004 1.52E−28 Cyp4a12a 6.66E−33 −0.456827492 0.317 0.597 1.65E−28 Coa6 7.34E−33 −0.411409685 0.15 0.373 1.82E−28 Sc5d 8.33E−33 −0.500900917 0.58 0.776 2.07E−28 Cd53 8.60E−33 0.265579528 0.103 0.003 2.13E−28 mt-Co3 1.07E−32 −0.705930608 0.346 0.603 2.65E−28 Cml2 1.08E−32 −0.397916138 0.647 0.857 2.68E−28 Gabarap 1.15E−32 −0.442546824 0.518 0.769 2.85E−28 Tns1 1.37E−32 0.434939232 0.403 0.196 3.40E−28 Fitm1 2.00E−32 −0.324153911 0.012 0.208 4.96E−28 B2m 2.22E−32 −0.330354919 0.871 0.963 5.52E−28 Chchd1 2.83E−32 −0.439819068 0.21 0.438 7.03E−28 Fcgr3 3.13E−32 0.308247077 0.107 0.004 7.76E−28 Tcerg1 3.42E−32 0.357549618 0.305 0.093 8.50E−28 C9 3.52E−32 −0.395507776 0.828 0.938 8.73E−28 Map2k3 4.21E−32 0.434654367 0.427 0.208 1.04E−27 Kdelr2 4.26E−32 0.397729248 0.484 0.355 1.06E−27 Litaf 5.05E−32 0.394366845 0.451 0.278 1.25E−27 Slc20a1 6.40E−32 0.357248475 0.284 0.076 1.59E−27 Mup14 8.41E−32 −0.697469805 0.358 0.616 2.09E−27 Maff 8.86E−32 0.355300257 0.224 0.048 2.20E−27 Tfpi2 9.96E−32 −0.366342462 0.155 0.39 2.47E−27 Aldob 1.09E−31 0.315339576 0.998 0.996 2.69E−27 Eif4g1 1.61E−31 0.374860037 0.723 0.669 4.01E−27 Cfp 1.68E−31 0.356178244 0.143 0.015 4.17E−27 Pbld1 1.90E−31 −0.442542986 0.315 0.565 4.73E−27 Dcxr 1.94E−31 −0.440851615 0.37 0.631 4.82E−27 Minos1 2.22E−31 −0.455548025 0.332 0.595 5.51E−27 Mug2 2.25E−31 0.368295871 0.776 0.738 5.60E−27 1110001J03Rik 2.82E−31 −0.432785224 0.215 0.456 7.01E−27 Tatdn2 2.96E−31 0.373296072 0.334 0.111 7.35E−27 Cmbl 4.73E−31 −0.442706435 0.415 0.678 1.18E−26 Ifitm3 4.74E−31 −0.425091425 0.587 0.812 1.18E−26 Adipor2 6.85E−31 −0.473791512 0.578 0.807 1.70E−26 Upb1 9.41E−31 −0.418695518 0.499 0.759 2.34E−26 Amacr 1.21E−30 −0.413582585 0.294 0.549 3.00E−26 Nr2f6 1.57E−30 −0.375433952 0.234 0.434 3.90E−26 Bcl3 1.68E−30 0.289017645 0.277 0.074 4.16E−26 Pigr 2.46E−30 0.348711695 0.947 0.947 6.10E−26 Chac2 3.07E−30 −0.286511682 0.057 0.251 7.62E−26 Uqcrh 3.79E−30 −0.429164519 0.589 0.81 9.41E−26 Lrrfip1 4.30E−30 0.445928709 0.37 0.156 1.07E−25 Ccs 8.22E−30 −0.426694207 0.42 0.676 2.04E−25 Atox1 9.01E−30 −0.446203219 0.382 0.633 2.24E−25 Wdr26 9.80E−30 0.432510772 0.549 0.406 2.43E−25 Mrp63 1.18E−29 −0.442201567 0.277 0.531 2.93E−25 Rnd3 1.20E−29 0.36548808 0.284 0.091 2.98E−25 Neat1 1.49E−29 0.63740381 0.31 0.135 3.71E−25 Bbox1 1.94E−29 −0.408245616 0.308 0.548 4.83E−25 Cyp39a1 2.10E−29 0.351128984 0.305 0.11 5.21E−25 Timm13 2.45E−29 −0.432961802 0.418 0.671 6.08E−25 Gclm 2.74E−29 0.269864161 0.695 0.712 6.80E−25 Sdc3 2.77E−29 0.359804895 0.103 0.005 6.89E−25 Acsl1 3.83E−29 −0.343424014 0.752 0.924 9.51E−25 Hint2 4.70E−29 −0.424321102 0.425 0.676 1.17E−24 1500011K16Rik 4.73E−29 −0.329639846 0.095 0.312 1.18E−24 Slc38a3 4.87E−29 −0.40978981 0.663 0.858 1.21E−24 Asgr1 4.98E−29 −0.385655364 0.656 0.851 1.24E−24 Vkorc1 5.02E−29 −0.404176916 0.296 0.54 1.25E−24 Cyp2j5 5.47E−29 −0.398305774 0.687 0.879 1.36E−24 H2-Eb1 5.57E−29 0.327872672 0.105 0.006 1.38E−24 Cyb5b 6.61E−29 −0.423345561 0.482 0.724 1.64E−24 2410015M20Rik 7.01E−29 −0.402123463 0.344 0.604 1.74E−24 Apobec1 7.36E−29 0.305082858 0.239 0.058 1.83E−24 Myl12a 8.33E−29 0.390780681 0.461 0.281 2.07E−24 Mybbp1a 8.99E−29 0.431161557 0.396 0.19 2.23E−24 Vsig4 9.72E−29 0.483290635 0.117 0.013 2.41E−24 H2-D1 1.04E−28 0.286522764 0.766 0.774 2.58E−24 Pfkfb2 1.32E−28 0.290016291 0.26 0.067 3.27E−24 Atp13a3 1.35E−28 0.394480252 0.532 0.41 3.36E−24 Commd6 1.55E−28 −0.364529559 0.172 0.39 3.85E−24 Serpina12 2.42E−28 −0.453399356 0.232 0.492 6.01E−24 Cfhr2 2.70E−28 −0.44846316 0.692 0.868 6.70E−24 Mup1 2.73E−28 −0.737727332 0.344 0.583 6.77E−24 Alad 3.06E−28 −0.420641438 0.286 0.513 7.60E−24 Glo1 3.46E−28 −0.406574019 0.513 0.749 8.60E−24 Psme1 4.27E−28 −0.394006165 0.26 0.5 1.06E−23 Zbtb20 4.83E−28 0.471532978 0.566 0.445 1.20E−23 Fpgs 5.94E−28 −0.34940945 0.146 0.348 1.48E−23 Ppan 6.61E−28 0.272410087 0.255 0.067 1.64E−23 Rpl13a 6.99E−28 −0.381462137 0.704 0.868 1.74E−23 Tmem56 7.12E−28 0.273557142 0.582 0.612 1.77E−23 Mpeg1 7.48E−28 0.493478112 0.263 0.089 1.86E−23 Gnl2 7.97E−28 0.390473036 0.384 0.171 1.98E−23 Rps18 8.83E−28 −0.488540797 0.337 0.578 2.19E−23 Gnas 9.32E−28 0.258853087 0.79 0.82 2.31E−23 Serbp1 1.38E−27 0.322652522 0.659 0.634 3.42E−23 Cyp2c54 1.66E−27 −0.39493764 0.499 0.759 4.12E−23 Hnrnpu 2.07E−27 0.339415607 0.625 0.582 5.14E−23 Bphl 2.18E−27 −0.40747923 0.339 0.579 5.40E−23 Cp 2.19E−27 0.254076812 0.89 0.943 5.44E−23 Etnppl 2.75E−27 0.41816318 0.706 0.606 6.83E−23 Nme1 3.88E−27 −0.432885306 0.425 0.622 9.63E−23 Nr1i3 3.91E−27 −0.412654588 0.165 0.377 9.71E−23 Slc4a4 5.25E−27 0.420259653 0.513 0.336 1.30E−22 0610005C13Rik 5.61E−27 −0.425135941 0.427 0.653 1.39E−22 Sds 5.65E−27 0.390741627 0.73 0.67 1.40E−22 Steap4 6.28E−27 0.437231109 0.37 0.222 1.56E−22 Mrps24 6.38E−27 −0.390380395 0.31 0.566 1.58E−22 Chd1 6.53E−27 0.378763061 0.377 0.166 1.62E−22 App 6.61E−27 0.361832458 0.315 0.114 1.64E−22 Ndufa3 6.89E−27 −0.41160475 0.344 0.598 1.71E−22 Hmgcr 6.96E−27 0.416711628 0.425 0.272 1.73E−22 Sptbn1 7.29E−27 0.42268289 0.439 0.26 1.81E−22 Acy3 7.41E−27 −0.313748988 0.131 0.332 1.84E−22 Tmem14c 8.44E−27 −0.368514287 0.332 0.585 2.10E−22 Arg1 8.49E−27 0.317948822 0.983 0.982 2.11E−22 Prrc2c 9.31E−27 0.439271845 0.415 0.201 2.31E−22 Hsp90ab1 9.80E−27 0.322748941 0.916 0.922 2.43E−22 Saa2 1.07E−26 0.558658405 0.315 0.222 2.66E−22 Usmg5 1.10E−26 −0.43049483 0.2 0.43 2.73E−22 Cyp2c68 1.26E−26 −0.398830868 0.298 0.558 3.13E−22 Gfra1 1.28E−26 0.386382804 0.599 0.498 3.18E−22 Por 1.45E−26 0.335963246 0.704 0.675 3.61E−22 Nop56 1.55E−26 0.265670844 0.282 0.084 3.85E−22 Hdac11 1.65E−26 −0.33684651 0.1 0.285 4.10E−22 Sparcl1 1.73E−26 −0.253616986 0 0.136 4.30E−22 Ndufa2 1.97E−26 −0.396473631 0.492 0.738 4.89E−22 Mmp14 2.07E−26 0.288913135 0.253 0.073 5.15E−22 Spp2 2.20E−26 −0.382096801 0.334 0.582 5.47E−22 Pecr 2.77E−26 −0.398084036 0.446 0.68 6.88E−22 Lmo4 2.79E−26 0.320534245 0.308 0.116 6.94E−22 Kmo 3.86E−26 −0.384440188 0.487 0.732 9.59E−22 Rps15 4.78E−26 −0.455155041 0.301 0.528 1.19E−21 Uhrf1bp1l 5.09E−26 0.419802385 0.399 0.207 1.26E−21 Igfbp2 5.12E−26 −0.298981027 0.68 0.885 1.27E−21 Acsm1 6.31E−26 −0.369245009 0.527 0.756 1.57E−21 Slc22a30 6.77E−26 −0.374598404 0.282 0.493 1.68E−21 Ddx6 6.90E−26 0.444275069 0.527 0.366 1.71E−21 Elovl5 7.23E−26 0.335236661 0.63 0.58 1.79E−21 Lrrc59 7.61E−26 0.377173076 0.422 0.28 1.89E−21 Gm23388 8.75E−26 0.416208382 0.222 0.057 2.17E−21 Ces3b 9.42E−26 −0.36637965 0.57 0.787 2.34E−21 Ccbl1 1.10E−25 −0.36488302 0.205 0.423 2.72E−21 Serinc3 1.16E−25 0.35928911 0.525 0.433 2.87E−21 Hdlbp 1.27E−25 0.345721467 0.737 0.713 3.14E−21 Akap13 1.55E−25 0.495253767 0.406 0.218 3.85E−21 Dkc1 1.58E−25 0.32575964 0.315 0.112 3.93E−21 Prdx4 1.64E−25 −0.417588892 0.372 0.607 4.08E−21 Slc35d1 2.13E−25 0.309435259 0.489 0.435 5.29E−21 Shmt1 2.34E−25 −0.393237106 0.339 0.556 5.80E−21 Hnrnpdl 2.40E−25 0.397994117 0.406 0.214 5.97E−21 Rps2 2.97E−25 −0.387862655 0.525 0.757 7.37E−21 Gne 2.99E−25 −0.425142761 0.263 0.469 7.41E−21 Ier5 3.24E−25 0.288994609 0.134 0.019 8.04E−21 Cebpa 3.27E−25 −0.39155301 0.442 0.672 8.13E−21 Gsk3b 3.56E−25 0.406458835 0.384 0.193 8.85E−21 Ddc 3.65E−25 −0.360752783 0.241 0.46 9.07E−21 Nr0b2 3.70E−25 −0.293010319 0.086 0.28 9.19E−21 Mettl20 3.72E−25 −0.331367185 0.119 0.327 9.23E−21 Ndufc2 4.83E−25 −0.425284817 0.36 0.579 1.20E−20 Fmo5 5.02E−25 0.286219883 0.823 0.837 1.25E−20 Uqcrb 6.09E−25 −0.408416744 0.425 0.641 1.51E−20 Slc40a1 6.95E−25 0.466969696 0.456 0.328 1.73E−20 Pdia6 7.01E−25 −0.389966782 0.47 0.712 1.74E−20 Tmem243 7.37E−25 −0.379053275 0.327 0.557 1.83E−20 Abhd14b 9.11E−25 −0.39366782 0.327 0.565 2.26E−20 D10Jhu81e 9.68E−25 −0.395730917 0.334 0.564 2.40E−20 Stom 9.70E−25 0.323229029 0.329 0.133 2.41E−20 Cox8a 1.39E−24 −0.399332537 0.396 0.621 3.45E−20 Gadd45g 1.42E−24 −0.355407686 0.375 0.639 3.53E−20 Wdr43 1.64E−24 0.343830267 0.353 0.146 4.08E−20 Timm8b 1.92E−24 −0.393581904 0.291 0.525 4.76E−20 Baz1a 2.07E−24 0.259610685 0.26 0.077 5.13E−20 Sfpq 2.16E−24 0.393977901 0.406 0.211 5.37E−20 Ucp2 2.17E−24 0.261164666 0.107 0.01 5.40E−20 Cisd1 2.20E−24 −0.372694857 0.451 0.686 5.47E−20 Mak16 2.52E−24 0.317126116 0.267 0.087 6.26E−20 Chuk 2.65E−24 0.372437977 0.523 0.421 6.57E−20 Cyp27a1 2.85E−24 −0.373510332 0.64 0.837 7.08E−20 Lcp1 3.45E−24 0.484011001 0.492 0.303 8.57E−20 Ivns1abp 3.73E−24 0.356610399 0.446 0.315 9.26E−20 Ptpn12 3.88E−24 0.33417878 0.263 0.084 9.63E−20 Tsc22d1 4.00E−24 −0.299728636 0.064 0.242 9.94E−20 Eef1a1 4.24E−24 0.282586942 0.835 0.85 1.05E−19 1110008F13Rik 5.38E−24 −0.37509166 0.411 0.648 1.34E−19 Cox6b1 6.04E−24 −0.362017449 0.594 0.809 1.50E−19 Akr1a1 6.54E−24 −0.326935362 0.671 0.857 1.62E−19 Gsr 6.57E−24 0.412829579 0.453 0.303 1.63E−19 Msn 8.02E−24 0.260172491 0.105 0.009 1.99E−19 Atp5g3 8.63E−24 −0.300221819 0.764 0.911 2.14E−19 Pxmp2 9.00E−24 −0.367129885 0.325 0.55 2.24E−19 Ifrd1 9.29E−24 0.490389826 0.365 0.185 2.31E−19 Atp5c1 1.13E−23 −0.347648538 0.587 0.792 2.82E−19 Cldn3 1.20E−23 −0.314469359 0.143 0.355 2.98E−19 Gstm4 1.23E−23 −0.380861133 0.234 0.444 3.06E−19 Gjb1 1.36E−23 −0.31656535 0.788 0.916 3.38E−19 Lap3 1.43E−23 −0.364371999 0.573 0.782 3.55E−19 Tpr 1.48E−23 0.440921219 0.501 0.339 3.67E−19 Smg1 1.87E−23 0.334990596 0.265 0.106 4.65E−19 Anp32a 1.90E−23 −0.316957742 0.193 0.413 4.71E−19 Purb 1.96E−23 0.35248294 0.341 0.158 4.88E−19 Dnaja2 1.97E−23 0.372342331 0.516 0.402 4.88E−19 AA474408 1.98E−23 0.347079511 0.274 0.094 4.90E−19 15-Sep 1.98E−23 −0.409167133 0.487 0.689 4.93E−19 Phc2 1.99E−23 0.31203626 0.284 0.111 4.93E−19 Apom 2.12E−23 −0.302410414 0.663 0.862 5.27E−19 Mrps18c 2.20E−23 −0.366291099 0.181 0.394 5.47E−19 Fcna 2.82E−23 0.377428055 0.124 0.02 7.01E−19 Ghr 2.91E−23 −0.364775879 0.647 0.833 7.23E−19 Mien1 3.12E−23 −0.370437762 0.27 0.489 7.74E−19 Palld 3.45E−23 0.341357023 0.353 0.167 8.57E−19 Cars 3.86E−23 0.315814572 0.329 0.135 9.57E−19 Hsd17b10 3.95E−23 −0.377206484 0.477 0.7 9.81E−19 Cyp3a13 4.37E−23 0.284411943 0.613 0.569 1.08E−18 Gm2788 4.67E−23 −0.283138796 0.072 0.264 1.16E−18 Cast 4.88E−23 0.400886525 0.399 0.213 1.21E−18 Mocs2 5.04E−23 −0.346681141 0.372 0.604 1.25E−18 Sirt3 5.14E−23 −0.345997558 0.203 0.413 1.28E−18 Hist1h1c 6.02E−23 −0.300906532 0.143 0.372 1.49E−18 Eprs 6.03E−23 0.37008595 0.566 0.488 1.50E−18 Tgoln1 6.08E−23 0.265747623 0.601 0.575 1.51E−18 Metap2 6.57E−23 0.368604828 0.453 0.285 1.63E−18 Hsp90b1 6.73E−23 −0.261479921 0.811 0.953 1.67E−18 Tmem258 6.87E−23 −0.27689533 0.115 0.282 1.70E−18 Adtrp 7.01E−23 −0.366413277 0.332 0.547 1.74E−18 Cideb 7.62E−23 −0.368365389 0.442 0.676 1.89E−18 Scd1 8.10E−23 −0.466125013 0.871 0.901 2.01E−18 Dgat2 8.46E−23 −0.343266251 0.558 0.767 2.10E−18 S100a1 9.78E−23 −0.374338118 0.453 0.661 2.43E−18 Echs1 1.11E−22 −0.331606352 0.642 0.817 2.76E−18 C8b 1.12E−22 −0.315917765 0.702 0.881 2.78E−18 Tgm2 1.18E−22 0.399330712 0.446 0.258 2.93E−18 BC005537 1.44E−22 0.354337911 0.544 0.45 3.57E−18 Zfp683 1.44E−22 −0.421689112 0 0.116 3.58E−18 Gyk 1.72E−22 0.368418571 0.465 0.35 4.28E−18 Cnpy2 1.77E−22 −0.372850093 0.365 0.566 4.41E−18 Ndufc1 1.95E−22 −0.344432714 0.291 0.515 4.83E−18 Cpt1a 1.98E−22 0.261119591 0.654 0.651 4.93E−18 Ethe1 2.35E−22 −0.333417645 0.286 0.49 5.84E−18 Bola3 2.38E−22 −0.368862428 0.313 0.525 5.91E−18 Tceb2 2.43E−22 −0.32073626 0.203 0.398 6.04E−18 3110043021Rik 2.85E−22 0.269386631 0.224 0.065 7.08E−18 Cyp2d40 3.06E−22 −0.321717407 0.181 0.35 7.61E−18 Car5a 3.09E−22 −0.308769058 0.153 0.331 7.68E−18 Cyp2c44 3.10E−22 −0.372953076 0.48 0.698 7.70E−18 Atp1b1 3.70E−22 0.370203015 0.391 0.226 9.18E−18 Map3k5 3.76E−22 0.33471162 0.346 0.147 9.34E−18 Ppp1r12a 3.85E−22 0.356295305 0.317 0.13 9.55E−18 Plk3 3.94E−22 0.416624571 0.413 0.226 9.77E−18 Huwe1 4.05E−22 0.387931325 0.492 0.314 1.01E−17 Zyx 4.49E−22 0.298338034 0.263 0.09 1.11E−17 Cep85l 5.28E−22 0.277893187 0.267 0.089 1.31E−17 Mup2 5.55E−22 −0.50447051 0.21 0.392 1.38E−17 Smdt1 5.76E−22 −0.367317155 0.351 0.573 1.43E−17 Sdhd 5.80E−22 −0.335261252 0.453 0.677 1.44E−17 Psmb3 6.50E−22 −0.330302519 0.153 0.345 1.62E−17 Lrrfip2 7.11E−22 0.373099277 0.384 0.185 1.77E−17 Oaz1 7.61E−22 −0.347228062 0.532 0.75 1.89E−17 Uqcc2 7.98E−22 −0.326858302 0.189 0.386 1.98E−17 Pnkd 8.25E−22 −0.292772175 0.153 0.327 2.05E−17 Csde1 8.37E−22 0.315554781 0.632 0.577 2.08E−17 Tcea3 8.56E−22 −0.355007815 0.236 0.439 2.13E−17 Ndufb8 8.67E−22 −0.348076577 0.539 0.746 2.15E−17 Kif21a 9.22E−22 0.404170578 0.461 0.293 2.29E−17 Bsg 1.04E−21 −0.31515012 0.58 0.797 2.59E−17 1810022K09Rik 1.09E−21 −0.300081452 0.107 0.301 2.71E−17 Proc 1.26E−21 −0.270719362 0.678 0.874 3.12E−17 Cldn2 1.28E−21 −0.251076838 0.036 0.202 3.17E−17 Acbd5 1.42E−21 −0.3952179 0.492 0.708 3.52E−17 Eif3c 1.44E−21 0.301979757 0.604 0.541 3.57E−17 Fkbp4 1.52E−21 −0.353366286 0.341 0.544 3.77E−17 Hibch 1.61E−21 −0.327130099 0.198 0.407 4.00E−17 Derl2 1.82E−21 −0.331734152 0.329 0.499 4.51E−17 Tob1 1.82E−21 −0.338705886 0.217 0.43 4.52E−17 Coq9 2.44E−21 −0.347936449 0.303 0.491 6.05E−17 Nop10 2.50E−21 −0.291908137 0.196 0.394 6.21E−17 Dnajc19 2.66E−21 −0.316006732 0.21 0.387 6.60E−17 Rps9 2.66E−21 −0.371793799 0.453 0.675 6.62E−17 Anxa5 2.76E−21 0.365372347 0.391 0.239 6.84E−17 Ubl5 2.91E−21 −0.303313218 0.186 0.383 7.23E−17 Paqr9 2.96E−21 −0.332341635 0.217 0.41 7.36E−17 Ndufa1 3.24E−21 −0.364515751 0.332 0.561 8.05E−17 Ndufv3 3.40E−21 −0.397145193 0.36 0.593 8.44E−17 Mcee 3.44E−21 −0.31991829 0.22 0.399 8.55E−17 Rps3 3.96E−21 −0.349320751 0.728 0.874 9.83E−17 Pxk 4.29E−21 0.281854648 0.303 0.116 1.07E−16 Cela1 4.38E−21 −0.272296838 0.129 0.304 1.09E−16 Ankrd11 4.39E−21 0.415626852 0.389 0.198 1.09E−16 C130074G19Rik 4.71E−21 −0.356338948 0.255 0.439 1.17E−16 Arl6ip1 4.97E−21 −0.364945533 0.42 0.643 1.23E−16 Ces1f 5.02E−21 −0.312589958 0.618 0.817 1.25E−16 Lsmd1 5.38E−21 −0.313140806 0.167 0.357 1.34E−16 Srsf11 5.96E−21 0.401209055 0.418 0.236 1.48E−16 Csrp3 6.66E−21 −0.293996249 0.098 0.256 1.65E−16 Edf1 6.81E−21 −0.381679393 0.492 0.703 1.69E−16 Ebp 7.00E−21 −0.355328266 0.446 0.666 1.74E−16 Eif4b 7.04E−21 0.36816236 0.542 0.438 1.75E−16 Ugt2a3 7.13E−21 −0.307528085 0.558 0.773 1.77E−16 Atf6 7.14E−21 0.377819844 0.432 0.273 1.77E−16 Gm24245 7.16E−21 0.546463773 0.422 0.214 1.78E−16 Nedd8 8.56E−21 −0.356380686 0.298 0.506 2.13E−16 AW112010 8.91E−21 −0.298104828 0.229 0.435 2.21E−16 Ndufs8 1.05E−20 −0.361439192 0.391 0.607 2.60E−16 Nucks1 1.28E−20 0.355785584 0.532 0.43 3.18E−16 Cybb 1.32E−20 0.377799564 0.107 0.031 3.27E−16 Pacsin2 1.33E−20 0.370825053 0.37 0.201 3.31E−16 Atp5o 1.63E−20 −0.331628292 0.487 0.712 4.05E−16 Rbm25 1.80E−20 0.421459678 0.461 0.296 4.47E−16 Pank1 1.90E−20 −0.352650118 0.475 0.704 4.71E−16 Il6ra 2.05E−20 0.304392668 0.332 0.142 5.08E−16 Dync1li1 2.16E−20 0.262406206 0.279 0.102 5.35E−16 Baat 2.16E−20 −0.308582001 0.575 0.767 5.36E−16 Slco1a1 2.33E−20 −0.362843757 0.599 0.777 5.79E−16 F10 2.54E−20 −0.271936054 0.723 0.895 6.30E−16 Bckdha 2.54E−20 −0.349979609 0.401 0.63 6.31E−16 Grhpr 2.65E−20 −0.353058662 0.568 0.774 6.57E−16 Mbl2 2.78E−20 −0.346518253 0.673 0.829 6.92E−16 AI182371 3.36E−20 −0.319894937 0.403 0.622 8.34E−16 Stk17b 3.58E−20 0.291050054 0.126 0.028 8.90E−16 Gcdh 3.65E−20 −0.300320098 0.668 0.85 9.07E−16 Atf4 3.83E−20 0.341134734 0.58 0.442 9.51E−16 Rnaseh2c 3.85E−20 −0.325683719 0.2 0.387 9.55E−16 Fus 3.95E−20 0.339324351 0.394 0.231 9.80E−16 Sbno1 4.29E−20 0.367100512 0.394 0.228 1.07E−15 Akap11 4.92E−20 0.346362286 0.351 0.164 1.22E−15 Tmbim6 5.47E−20 −0.271070995 0.852 0.942 1.36E−15 Rsl1d1 5.47E−20 0.346056141 0.47 0.338 1.36E−15 Hspa5 6.17E−20 0.268221373 0.914 0.944 1.53E−15 Cebpb 6.42E−20 −0.361738286 0.286 0.45 1.59E−15 Sar1b 7.27E−20 −0.307930709 0.568 0.772 1.80E−15 Tmem242 7.52E−20 −0.272538433 0.146 0.308 1.87E−15 Selk 8.09E−20 −0.338314398 0.308 0.486 2.01E−15 Psmb1 8.35E−20 −0.358482353 0.575 0.759 2.07E−15 Cxcl1 8.55E−20 0.370070418 0.444 0.314 2.12E−15 Larp4b 9.26E−20 0.34214672 0.453 0.281 2.30E−15 Tm7sf2 9.70E−20 −0.316381125 0.325 0.52 2.41E−15 Pvrl2 1.04E−19 −0.261260991 0.11 0.241 2.59E−15 Pi4k2a 1.06E−19 0.353561144 0.425 0.32 2.62E−15 Gm4951 1.10E−19 −0.322087312 0.284 0.491 2.73E−15 Gm10800 1.24E−19 0.562597493 0.115 0.019 3.07E−15 Mpc1 1.29E−19 −0.280163495 0.203 0.369 3.21E−15 Ctsc 1.32E−19 0.361021766 0.403 0.271 3.29E−15 Scaf11 1.37E−19 0.359845436 0.449 0.295 3.40E−15 Bhmt2 1.46E−19 −0.311413339 0.427 0.637 3.63E−15 Dnajc5 1.48E−19 0.326483514 0.372 0.223 3.69E−15 Mrpl12 1.58E−19 −0.308200176 0.37 0.583 3.94E−15 Anapc13 1.82E−19 −0.364181956 0.253 0.427 4.52E−15 Sdhb 2.13E−19 −0.289642823 0.604 0.797 5.30E−15 Ndufb3 2.19E−19 −0.327185415 0.246 0.43 5.45E−15 Ptp4a1 3.01E−19 0.262691158 0.334 0.145 7.47E−15 Rps21 3.54E−19 −0.364450868 0.358 0.579 8.79E−15 Fam214a 3.55E−19 −0.265769677 0.074 0.248 8.82E−15 Dhx9 3.61E−19 0.350364065 0.427 0.252 8.96E−15 Shb 3.75E−19 0.315236194 0.382 0.204 9.32E−15 0610011F06Rik 4.40E−19 −0.303688511 0.425 0.653 1.09E−14 Mdm2 4.71E−19 0.328296258 0.305 0.138 1.17E−14 Nedd41 4.76E−19 0.281232817 0.332 0.147 1.18E−14 Tmem106b 4.85E−19 0.280204492 0.58 0.557 1.21E−14 Bet1 5.02E−19 −0.296563627 0.203 0.381 1.25E−14 Rps10 5.49E−19 −0.33690905 0.239 0.453 1.36E−14 Myo1b 5.63E−19 0.262427327 0.563 0.542 1.40E−14 Kpna1 5.71E−19 0.32304803 0.363 0.206 1.42E−14 Slc2a2 5.98E−19 −0.312348392 0.263 0.479 1.48E−14 Sdr9c7 6.14E−19 −0.259988635 0.105 0.284 1.52E−14 Hipk3 6.37E−19 0.339385214 0.396 0.223 1.58E−14 Fam25c 6.60E−19 −0.297673676 0.158 0.356 1.64E−14 Prdx5 6.78E−19 −0.28208825 0.673 0.834 1.68E−14 Otc 8.10E−19 −0.29903416 0.78 0.914 2.01E−14 Apc 8.43E−19 0.27896726 0.317 0.133 2.09E−14 mmu-mir-6236 8.51E−19 0.520569164 0.831 0.837 2.11E−14 Jhdm1d 8.85E−19 0.304101624 0.279 0.112 2.20E−14 Net1 8.95E−19 0.34785505 0.408 0.27 2.22E−14 Romo1 9.12E−19 −0.335854841 0.248 0.446 2.26E−14 Sgk1 9.28E−19 0.284303028 0.21 0.085 2.30E−14 Tmem160 9.41E−19 −0.339044834 0.205 0.385 2.34E−14 Acot13 9.58E−19 −0.288638646 0.241 0.401 2.38E−14 Sc4mol 9.81E−19 −0.326170476 0.444 0.642 2.44E−14 Tbl1xr1 1.14E−18 0.307509115 0.341 0.176 2.84E−14 Dync1h1 1.27E−18 0.379607116 0.379 0.21 3.17E−14 Ak2 1.49E−18 −0.345102135 0.458 0.66 3.71E−14 Mrc1 1.63E−18 0.340444916 0.131 0.03 4.05E−14 Slc41a2 1.74E−18 0.260152635 0.298 0.134 4.31E−14 Fbxo21 1.75E−18 −0.263087536 0.131 0.298 4.34E−14 Mki67ip 1.78E−18 0.318372964 0.344 0.171 4.41E−14 Nudt4 1.91E−18 0.25418892 0.594 0.568 4.75E−14 Mettl7a1 1.93E−18 −0.322098553 0.465 0.682 4.79E−14 Aox3 1.96E−18 −0.333319828 0.764 0.894 4.88E−14 1110058L19Rik 2.07E−18 −0.258088587 0.129 0.281 5.15E−14 Smap2 2.29E−18 0.348911433 0.363 0.184 5.69E−14 Hmgcs1 2.30E−18 −0.349112403 0.53 0.703 5.71E−14 Apcs 2.69E−18 0.298925674 0.551 0.525 6.67E−14 Tmem86b 2.75E−18 −0.258236533 0.167 0.299 6.83E−14 Txn1 2.82E−18 −0.309123787 0.642 0.809 7.01E−14 Mvd 2.84E−18 −0.270409867 0.112 0.269 7.04E−14 Psmb6 3.03E−18 −0.319377533 0.477 0.683 7.54E−14 Cpb2 3.15E−18 −0.321495225 0.635 0.813 7.81E−14 Glyctk 3.45E−18 −0.297701904 0.251 0.466 8.56E−14 Mrpl42 3.66E−18 −0.284507519 0.215 0.386 9.09E−14 Bnip3 3.73E−18 −0.336168189 0.348 0.55 9.26E−14 Slirp 3.82E−18 −0.308519262 0.205 0.39 9.48E−14 2010107E04Rik 4.44E−18 −0.318247806 0.473 0.681 1.10E−13 Sec61b 4.97E−18 −0.290284119 0.232 0.437 1.24E−13 Sigmar1 5.19E−18 −0.305468332 0.353 0.514 1.29E−13 Cyp2b10 5.48E−18 −0.517460658 0.422 0.542 1.36E−13 Mdh1 5.75E−18 −0.307657821 0.747 0.887 1.43E−13 Dhdh 6.02E−18 −0.334814135 0.377 0.583 1.49E−13 Ptpn2 6.03E−18 0.273418437 0.255 0.097 1.50E−13 Cyp2c55 6.35E−18 −0.290435372 0.076 0.243 1.58E−13 Cfhr1 6.80E−18 −0.325332852 0.384 0.572 1.69E−13 Bptf 7.62E−18 0.324463857 0.332 0.155 1.89E−13 Yap1 7.96E−18 0.328109852 0.375 0.207 1.98E−13 Rexo2 8.64E−18 −0.3263129 0.387 0.578 2.15E−13 Akr1e1 9.43E−18 −0.258207619 0.167 0.299 2.34E−13 Tjp1 9.51E−18 0.286163863 0.251 0.096 2.36E−13 Cyp4f15 9.51E−18 −0.299840345 0.241 0.428 2.36E−13 Naprt1 1.22E−17 −0.338143058 0.317 0.492 3.03E−13 Slco1a4 1.39E−17 0.313739505 0.387 0.238 3.44E−13 Rab6a 1.49E−17 0.32343226 0.461 0.335 3.69E−13 Slc10a1 1.54E−17 −0.325757408 0.695 0.843 3.82E−13 Ipo7 1.64E−17 0.324580152 0.334 0.168 4.06E−13 Cyp4f14 1.75E−17 −0.295933211 0.387 0.6 4.35E−13 Tnks2 1.84E−17 0.317626402 0.358 0.197 4.57E−13 Macf1 1.95E−17 0.404177263 0.377 0.219 4.84E−13 Esd 2.01E−17 −0.280760023 0.601 0.784 4.98E−13 Bst2 2.09E−17 −0.315565973 0.346 0.54 5.20E−13 Stbd1 2.72E−17 −0.273216024 0.181 0.362 6.74E−13 Abcc2 2.91E−17 0.289681267 0.632 0.612 7.23E−13 Aqp9 3.28E−17 −0.310863805 0.434 0.647 8.15E−13 Ddx3y 3.39E−17 0.339517654 0.47 0.353 8.42E−13 Pet100 3.40E−17 −0.28003555 0.172 0.339 8.44E−13 Agpat2 3.42E−17 −0.298159013 0.437 0.638 8.49E−13 Fah 3.50E−17 −0.259255187 0.652 0.834 8.70E−13 Tmem147 3.77E−17 −0.283785217 0.301 0.491 9.36E−13 Sf1 3.87E−17 0.30230624 0.351 0.176 9.61E−13 Ddah1 4.14E−17 −0.312000429 0.301 0.482 1.03E−12 Tmem37 4.76E−17 −0.282207793 0.253 0.44 1.18E−12 Dhrs4 5.12E−17 −0.332074421 0.492 0.69 1.27E−12 Mrp133 5.59E−17 −0.265447876 0.241 0.419 1.39E−12 Pik3c2a 6.36E−17 0.324870962 0.341 0.198 1.58E−12 Acads 6.69E−17 −0.32421998 0.341 0.539 1.66E−12 D17Wsu92e 7.50E−17 0.252482331 0.601 0.588 1.86E−12 Coro1c 7.89E−17 0.306679199 0.208 0.068 1.96E−12 Aadat 8.39E−17 −0.318627951 0.329 0.507 2.08E−12 Rlim 8.53E−17 0.31023282 0.305 0.142 2.12E−12 Sult1d1 8.95E−17 −0.316458159 0.492 0.684 2.22E−12 Mrpl34 9.07E−17 −0.283750306 0.215 0.361 2.25E−12 Tspo 1.02E−16 −0.315729205 0.313 0.506 2.54E−12 Fdps 1.07E−16 −0.266347718 0.248 0.445 2.67E−12 Sdsl 1.11E−16 0.259290764 0.303 0.137 2.77E−12 Nrp1 1.16E−16 0.360791537 0.391 0.253 2.88E−12 0610007P14Rik 1.21E−16 −0.257015045 0.184 0.346 3.00E−12 Abcd3 1.26E−16 −0.271805105 0.728 0.879 3.13E−12 Etnk1 1.34E−16 0.315992963 0.442 0.328 3.33E−12 Actn4 1.35E−16 0.312388865 0.53 0.425 3.35E−12 Chmp4b 1.39E−16 0.300153098 0.442 0.301 3.46E−12 Gadd45gip1 1.50E−16 −0.304090556 0.22 0.4 3.73E−12 Mrpl11 1.53E−16 −0.268482417 0.186 0.345 3.80E−12 Ndufs4 1.68E−16 −0.313160933 0.391 0.562 4.17E−12 Tmem150a 1.70E−16 −0.253507791 0.172 0.335 4.21E−12 Mrpl15 1.77E−16 −0.291228504 0.236 0.415 4.39E−12 Ipo5 1.94E−16 0.268735631 0.277 0.117 4.82E−12 Atp2b1 2.09E−16 0.332096305 0.334 0.172 5.18E−12 Erbb2ip 2.14E−16 0.333163506 0.489 0.364 5.31E−12 Amy1 2.20E−16 −0.282967905 0.463 0.676 5.45E−12 Mrpl41 2.22E−16 −0.267412137 0.174 0.348 5.50E−12 Kif1b 2.36E−16 0.371764707 0.527 0.435 5.86E−12 Birc6 2.38E−16 0.344367807 0.446 0.28 5.91E−12 Agxt 2.44E−16 −0.258383387 0.601 0.789 6.06E−12 Rpl13 2.49E−16 −0.298816085 0.294 0.464 6.18E−12 Pgls 2.72E−16 −0.274714156 0.22 0.345 6.74E−12 Ndufv2 2.72E−16 −0.327639406 0.461 0.648 6.75E−12 Ndufb10 3.33E−16 −0.300358086 0.489 0.681 8.26E−12 Myeov2 3.91E−16 −0.305189789 0.303 0.48 9.72E−12 Supt6 4.06E−16 0.291294768 0.291 0.137 1.01E−11 Cxcl12 4.35E−16 −0.305838679 0.251 0.419 1.08E−11 Aldh4a1 4.68E−16 −0.29070878 0.425 0.613 1.16E−11 Apof 4.96E−16 −0.252173807 0.759 0.897 1.23E−11 Rap1b 5.54E−16 0.340766029 0.406 0.258 1.38E−11 Acaa1a 5.73E−16 −0.301848759 0.475 0.679 1.42E−11 Pak2 5.87E−16 0.281467155 0.308 0.143 1.46E−11 Tspan31 5.99E−16 −0.295881364 0.415 0.622 1.49E−11 Ubr4 6.49E−16 0.330144527 0.411 0.25 1.61E−11 Bdh1 7.35E−16 −0.293611347 0.315 0.49 1.82E−11 Cap1 7.77E−16 0.325055169 0.356 0.202 1.93E−11 Syncrip 8.09E−16 0.27476476 0.365 0.198 2.01E−11 Nrip1 8.50E−16 0.272854584 0.246 0.097 2.11E−11 Tmprss6 8.97E−16 −0.280234101 0.551 0.738 2.23E−11 Commd3 9.66E−16 −0.265556375 0.274 0.45 2.40E−11 Il13ra1 1.20E−15 0.278527191 0.294 0.143 2.99E−11 Tab2 1.24E−15 0.348412001 0.425 0.3 3.07E−11 Bzw1 1.26E−15 0.294810535 0.475 0.344 3.12E−11 Arhgap5 1.28E−15 0.264043476 0.506 0.454 3.18E−11 Rpl14 1.45E−15 −0.277637754 0.372 0.574 3.61E−11 Clic4 1.62E−15 0.299795775 0.368 0.221 4.01E−11 Lgals9 1.79E−15 −0.269998113 0.621 0.793 4.44E−11 Mrpl20 2.03E−15 −0.309348635 0.301 0.489 5.03E−11 C1d 2.60E−15 −0.255261652 0.208 0.354 6.45E−11 Alcam 2.79E−15 0.323788815 0.396 0.26 6.92E−11 Mapk6 2.93E−15 0.256831906 0.303 0.145 7.27E−11 Mrpl28 2.99E−15 −0.269896048 0.229 0.378 7.42E−11 Fam195a 3.00E−15 −0.264890901 0.205 0.373 7.46E−11 Aes 3.03E−15 −0.264214993 0.535 0.729 7.53E−11 Gstk1 3.20E−15 −0.282802747 0.351 0.532 7.93E−11 Snx10 3.26E−15 0.285642594 0.341 0.188 8.10E−11 Plcxd2 3.73E−15 −0.275192522 0.162 0.332 9.27E−11 Park7 3.77E−15 −0.260230015 0.601 0.784 9.36E−11 Med13 4.26E−15 0.294918978 0.325 0.168 1.06E−10 Btaf1 4.29E−15 0.275463861 0.284 0.138 1.07E−10 Spcs1 4.65E−15 −0.26287037 0.236 0.413 1.16E−10 Abcf1 5.59E−15 0.303190272 0.458 0.315 1.39E−10 Selo 5.68E−15 −0.257421903 0.217 0.381 1.41E−10 Usp9x 5.80E−15 0.318385696 0.451 0.299 1.44E−10 Klf3 5.86E−15 0.267357487 0.301 0.146 1.45E−10 Iah1 5.99E−15 −0.292985785 0.446 0.612 1.49E−10 Il4ra 6.47E−15 0.25739098 0.248 0.102 1.61E−10 Acat3 6.81E−15 −0.311510623 0.427 0.6 1.69E−10 Ugt3a2 7.27E−15 −0.258613351 0.492 0.689 1.80E−10 PM20l1 8.41E−15 0.308488005 0.372 0.212 2.09E−10 Abcb11 8.50E−15 −0.261778471 0.618 0.791 2.11E−10 Pkp4 8.99E−15 0.323033636 0.401 0.258 2.23E−10 Cbr1 1.14E−14 0.284717454 0.494 0.395 2.84E−10 Deb1 1.16E−14 −0.267029156 0.274 0.443 2.87E−10 Akr1d1 1.31E−14 −0.278865899 0.332 0.515 3.24E−10 Rangap1 1.35E−14 0.296226768 0.387 0.244 3.36E−10 Rmnd5a 1.44E−14 0.318903459 0.47 0.352 3.57E−10 Psma6 1.49E−14 −0.30353658 0.501 0.675 3.71E−10 Nqo2 1.50E−14 −0.267802053 0.317 0.486 3.73E−10 Rpl34 1.53E−14 −0.297598539 0.246 0.398 3.81E−10 Rnf169 1.61E−14 0.333974467 0.315 0.173 4.00E−10 Hpn 1.64E−14 −0.268601326 0.406 0.604 4.07E−10 Plin5 1.64E−14 0.296281512 0.456 0.315 4.07E−10 Abcg2 1.68E−14 −0.280923445 0.294 0.466 4.17E−10 Pa2g4 1.82E−14 0.289349263 0.492 0.418 4.53E−10 Sf3b1 1.91E−14 0.28884767 0.508 0.406 4.75E−10 Serpina3c 1.99E−14 −0.287011328 0.258 0.385 4.94E−10 Swi5 2.17E−14 −0.262086804 0.341 0.501 5.38E−10 Hsbp1 2.27E−14 −0.286726926 0.329 0.498 5.65E−10 Sema4g 2.43E−14 −0.250459516 0.27 0.451 6.04E−10 Gtf2a2 2.63E−14 0.279207862 0.379 0.237 6.54E−10 Gcat 2.78E−14 −0.258728349 0.315 0.49 6.91E−10 Ccdc50 2.83E−14 0.285830087 0.401 0.246 7.02E−10 Ldlr 2.90E−14 0.282025946 0.432 0.364 7.20E−10 Srrm2 3.29E−14 0.328159189 0.456 0.313 8.16E−10 Suco 3.46E−14 0.250962583 0.26 0.113 8.60E−10 Mapkapk2 3.50E−14 0.31382654 0.396 0.254 8.68E−10 Tbca 3.66E−14 −0.27261031 0.284 0.401 9.08E−10 Slc26a1 3.68E−14 −0.28165635 0.329 0.495 9.13E−10 Acsm5 3.73E−14 −0.261394035 0.236 0.397 9.27E−10 Eif3a 3.77E−14 0.314713983 0.542 0.461 9.36E−10 Mrps12 4.19E−14 −0.250441318 0.193 0.332 1.04E−09 St3gal4 4.22E−14 0.275033534 0.368 0.244 1.05E−09 mt-Atp6 4.35E−14 −0.47818742 0.305 0.452 1.08E−09 Dera 4.65E−14 −0.267441985 0.32 0.49 1.15E−09 Slc25a10 4.71E−14 −0.282805644 0.351 0.536 1.17E−09 Plbd2 4.76E−14 0.264873115 0.344 0.199 1.18E−09 Hectd1 5.23E−14 0.30802968 0.547 0.476 1.30E−09 Srd5a1 6.05E−14 −0.277347272 0.308 0.464 1.50E−09 Ubb 6.13E−14 −0.275030382 0.265 0.45 1.52E−09 Mlycd 7.23E−14 −0.290948387 0.329 0.503 1.80E−09 Cep85 7.37E−14 0.28389234 0.313 0.167 1.83E−09 Pdzd8 8.19E−14 0.286270568 0.36 0.206 2.03E−09 Ddx27 8.44E−14 0.252155421 0.286 0.133 2.09E−09 Kdm5a 8.92E−14 0.351390096 0.308 0.157 2.22E−09 Ptpn11 1.04E−13 0.277804552 0.37 0.218 2.58E−09 Trib1 1.05E−13 0.331693479 0.411 0.308 2.61E−09 2810428I15Rik 1.10E−13 −0.263117928 0.2 0.349 2.74E−09 Sptan1 1.23E−13 0.312663889 0.348 0.21 3.05E−09 Gldc 1.23E−13 0.280156601 0.465 0.375 3.07E−09 Impad1 1.37E−13 0.32267465 0.391 0.263 3.41E−09 Gch1 1.38E−13 −0.269053605 0.461 0.643 3.42E−09 Rps24 1.49E−13 −0.262473665 0.453 0.637 3.71E−09 Dcaf11 1.51E−13 −0.281659388 0.446 0.617 3.76E−09 Rraga 1.66E−13 0.262613483 0.337 0.196 4.13E−09 Furin 2.01E−13 0.253587917 0.477 0.417 4.99E−09 Golga4 2.01E−13 0.352084678 0.427 0.31 5.00E−09 Ppp2r5a 2.19E−13 −0.260504538 0.43 0.594 5.43E−09 Arpc1b 2.20E−13 0.259676842 0.263 0.119 5.46E−09 Acsl4 2.24E−13 0.298529302 0.427 0.323 5.55E−09 Lipc 2.28E−13 −0.254841484 0.401 0.59 5.65E−09 Diap1 3.27E−13 0.325941798 0.382 0.241 8.12E−09 Rabac1 3.43E−13 −0.265987205 0.346 0.524 8.51E−09 Pmpcb 3.44E−13 −0.263615722 0.356 0.536 8.55E−09 Mgea5 3.67E−13 0.32630901 0.413 0.268 9.10E−09 Slc16a10 3.80E−13 −0.254826191 0.196 0.315 9.44E−09 Ppara 3.86E−13 −0.287133273 0.234 0.407 9.59E−09 Usp4 4.19E−13 0.279964381 0.439 0.286 1.04E−08 Ptpmt1 4.26E−13 −0.255981462 0.372 0.546 1.06E−08 Psma1 4.43E−13 −0.256671259 0.353 0.521 1.10E−08 Ythdc1 4.81E−13 0.264130576 0.301 0.15 1.19E−08 Abce1 4.88E−13 0.279955892 0.437 0.31 1.21E−08 Ppip5k2 4.98E−13 0.320939415 0.344 0.197 1.24E−08 Ftsj3 5.57E−13 0.255227431 0.346 0.191 1.38E−08 Tpi1 5.58E−13 −0.26157943 0.539 0.706 1.38E−08 Slc16a2 5.92E−13 −0.251969763 0.255 0.412 1.47E−08 Ubr5 6.17E−13 0.305718363 0.399 0.248 1.53E−08 Il6st 6.32E−13 0.316786986 0.411 0.273 1.57E−08 Xrn2 6.73E−13 0.298471923 0.387 0.245 1.67E−08 Cdh1 6.96E−13 0.269696738 0.327 0.202 1.73E−08 Nek7 9.74E−13 0.291098417 0.394 0.271 2.42E−08 Slc25a51 9.95E−13 0.263985158 0.308 0.161 2.47E−08 Magi3 1.02E−12 0.269961841 0.303 0.156 2.54E−08 Pde3b 1.14E−12 −0.258970093 0.243 0.376 2.82E−08 Megf9 1.14E−12 0.276890033 0.289 0.158 2.82E−08 Zfp106 1.96E−12 0.336920255 0.391 0.254 4.87E−08 Gstm3 2.40E−12 −0.411092337 0.265 0.414 5.97E−08 Sars 2.65E−12 0.276853119 0.43 0.322 6.58E−08 Psap 3.18E−12 0.257800256 0.556 0.513 7.90E−08 Trip11 3.20E−12 0.347886673 0.341 0.2 7.94E−08 Naa50 3.28E−12 0.265659058 0.444 0.358 8.14E−08 Prpf19 3.66E−12 0.25876049 0.432 0.315 9.09E−08 Pcm1 4.11E−12 0.265397644 0.274 0.142 1.02E−07 Papss2 4.45E−12 −0.254475327 0.337 0.507 1.10E−07 Coasy 5.10E−12 −0.253428655 0.327 0.475 1.27E−07 Actr3 5.91E−12 0.275997927 0.36 0.233 1.47E−07 Ccnl1 6.84E−12 0.256623048 0.351 0.206 1.70E−07 Hipk1 6.86E−12 0.291600227 0.337 0.195 1.70E−07 Riok3 6.99E−12 0.291562038 0.43 0.345 1.74E−07 Pdia4 7.20E−12 −0.27191836 0.43 0.595 1.79E−07 Nploc4 7.73E−12 0.291804954 0.351 0.214 1.92E−07 Dsp 8.13E−12 0.265533344 0.32 0.178 2.02E−07 Spag9 8.42E−12 0.318820155 0.415 0.286 2.09E−07 Map3k2 9.41E−12 0.251791147 0.265 0.131 2.34E−07 Gars 1.75E−11 0.257638792 0.334 0.199 4.33E−07 Arhgdia 1.94E−11 0.256326455 0.317 0.186 4.81E−07 Gcgr 2.44E−11 −0.257636913 0.446 0.609 6.06E−07 Eif4ebp1 3.67E−11 0.261682735 0.387 0.283 9.11E−07 Sco2 3.81E−11 −0.260508515 0.353 0.508 9.46E−07 Zfp259 3.89E−11 0.255636639 0.32 0.182 9.66E−07 Rbm39 3.97E−11 0.265732671 0.506 0.42 9.85E−07 Zfand5 4.18E−11 0.28815165 0.401 0.293 1.04E−06 Usp7 4.52E−11 0.287320099 0.363 0.241 1.12E−06 Eif4a1 5.11E−11 0.251906299 0.418 0.291 1.27E−06 Herc1 6.98E−11 0.256188826 0.246 0.122 1.73E−06 Gm5424 1.56E−10 0.269800095 0.411 0.3 3.88E−06 Ndufa5 1.58E−10 −0.251988986 0.418 0.567 3.93E−06 Ctnnd1 2.19E−10 0.251848095 0.358 0.217 5.45E−06 Cul3 2.70E−10 0.278802183 0.415 0.303 6.69E−06 4932438A13Rik 2.79E−10 0.287850722 0.329 0.203 6.93E−06 Usp34 2.86E−10 0.285942387 0.37 0.243 7.10E−06 Ppm1g 3.21E−10 0.252225215 0.358 0.221 7.96E−06 Smoc1 3.30E−10 0.26157412 0.368 0.238 8.20E−06 Erf3b 3.93E−10 0.250328103 0.449 0.366 9.77E−06 Gadd45a 4.63E−10 0.282867411 0.251 0.149 1.15E−05 Cul1 4.87E−10 0.259206487 0.425 0.313 1.21E−05 Eea1 5.07E−10 0.261201113 0.363 0.245 1.26E−05 Tln1 5.68E−10 0.321033046 0.31 0.202 1.41E−05 Rassf3 6.24E−10 0.291236708 0.422 0.319 1.55E−05 Herc4 8.92E−10 0.267474882 0.332 0.217 2.21E−05 4931406C07Rik 9.77E−10 −0.254363633 0.616 0.748 2.43E−05 Slc30a1 1.09E−09 0.250570123 0.346 0.238 2.72E−05 Gstp1 1.77E−09 −0.264374672 0.685 0.822 4.40E−05 Bclaf1 3.63E−09 0.26848767 0.372 0.256 9.01E−05 Gnai2 6.70E−09 0.281667665 0.391 0.31 0.000166446 Gm20594 1.18E−08 0.295686612 0.442 0.294 0.000292421 Ash1l 1.18E−08 0.265693821 0.301 0.175 0.000293692 Rock1 1.47E−07 0.2607635 0.413 0.308 0.003638685 Gda 9.30E−07 0.266276129 0.243 0.165 0.02310523 Ftl1 1.58E−06 −0.26029441 0.317 0.409 0.039229795 Gm23935 5.53E−06 0.424222263 0.878 0.925 0.137419547

TABLE 3 Differentially expressed genes between time point A24 and untreated (UT). ID p_val avg_logFC pct.1 pct.2 p_val_adj Gm15564 0 1.820580657 0.982 0.956 0 Lars2 0 1.711400221 0.998 0.994 0 Gm26924 0 1.419027502 1 1 0 Sephs2 0 0.889992859 0.949 0.761 0 Grip2 0 0.877868293 0.475 0.002 0 Fgl1 0 0.864933885 0.938 0.784 0 Fga 0 0.828543313 0.998 0.997 0 Fgb 0 0.744973762 1 1 0 Fgg 0 0.680530925 0.999 0.991 0 Apoa2 0 −0.545518454 0.997 1 0 mt-Rnr2 0 −0.778341998 1 1 0 Mup3 0 −0.806219448 0.998 1 0 mt-Nd2 0 −1.241926048 0.949 0.999 0 mt-Nd5 0 −1.383591054 0.869 0.995 0 mt-Nd1 0 −1.419683574 0.942 1 0 mt-Co1 0 −1.43342755 0.949 0.999 0 mt-Cytb 0 −1.571232911 0.926 0.999 0 Mup11 0 −1.611434806 0.873 1 0 Mup19 0 −1.699352699 0.916 1 0 Mup18 0 −1.727178347 0.769 0.997 0 Mup17 0 −1.800348604 0.938 1 0 Mup9 0 −1.847446915 0.619 0.976 0 mt-Nd4 0 −1.957424825 0.849 0.998 0 Ankrd55 2.80898674204367e−314 −1.8735659 0.11 0.696 6.97527587784284e−310 Acaa1b 4.58424219320629e−311 −0.85084133 0.757 0.969  1.14E−306 mt-Co2  2.73E−303 −1.396543228 0.034 0.629  6.78E−299 Serpina1a  1.18E−299 −0.675201963 0.924 0.991  2.93E−295 n-R5-8s1  6.16E−298 1.252818829 0.522 0.031  1.53E−293 Gpx1  2.33E−291 −0.50797139 0.977 0.999  5.78E−287 Apoe  1.69E−261 −0.421271729 1 1  4.18E−257 Mup6  1.39E−251 −1.678184828 0.795 0.992  3.44E−247 Cyb5  3.79E−249 −0.704808492 0.955 0.983  9.41E−245 Gm24601  1.30E−237 0.984391691 0.404 0.015  3.24E−233 Sepp1  6.71E−231 0.448586822 1 1  1.67E−226 Mup16  6.04E−222 −1.018975936 0.615 0.934  1.50E−217 Hyou1  1.76E−219 0.846484822 0.717 0.385  4.36E−215 Gm13775  1.79E−215 −1.032451941 0.306 0.761  4.43E−211 mt-Co3  2.31E−212 −1.167027737 0.115 0.603  5.73E−208 Serpina1d  3.91E−207 −0.494007182 0.946 0.988  9.71E−203 Hspa5  9.23E−204 0.610549064 0.974 0.944  2.29E−199 Ugt2b5  1.22E−199 −0.576498765 0.893 0.959  3.03E−195 Gsta3  6.18E−189 −0.66935487 0.925 0.956  1.54E−184 Cyp2d9  1.16E−183 −0.567166215 0.896 0.959  2.89E−179 Mup15  4.07E−182 −1.234928375 0.173 0.617  1.01E−177 Pdia3  8.53E−181 0.593769188 0.895 0.797  2.12E−176 Mup5  5.23E−180 −1.370621307 0.47 0.839  1.30E−175 Apoc3  7.62E−179 −0.440433124 0.952 0.993  1.89E−174 Serpina1c  1.69E−176 −0.402626732 0.983 0.998  4.19E−172 Calr  1.06E−174 0.555145472 0.952 0.885  2.64E−170 Cyp2b10  5.60E−174 −1.164490931 0.174 0.542  1.39E−169 Hamp  6.04E−172 −0.826148443 0.552 0.884  1.50E−167 Hsp90b1  1.49E−166 0.534208217 0.954 0.953  3.69E−162 Fn1  5.06E−157 0.699634526 0.905 0.821  1.26E−152 Scd1  6.56E−157 0.726687286 0.98 0.901  1.63E−152 Uqcrq  9.90E−156 −0.595921048 0.856 0.951  2.46E−151 Itih4  2.62E−154 0.525074867 0.974 0.948  6.50E−150 Cyp3a11  8.42E−152 −0.363891177 0.99 1  2.09E−147 Apoc1  4.19E−149 −0.380336769 0.976 0.999  1.04E−144 Hp  1.00E−142 0.431328341 0.998 0.999  2.49E−138 Elovl3  2.48E−142 −0.675967012 0.54 0.827  6.15E−138 Mup4  1.89E−139 −1.087038527 0.616 0.898  4.70E−135 mt-Rnr1  7.20E−137 −0.456211361 1 1  1.79E−132 Bhmt  8.82E−137 −0.520184894 0.868 0.956  2.19E−132 Mup21  6.83E−134 −0.697735774 0.706 0.929  1.70E−129 Serpina10  5.36E−129 0.565046404 0.813 0.641  1.33E−124 Ahcy  3.96E−128 −0.562968597 0.73 0.916  9.83E−124 Hdlbp  4.80E−125 0.565147241 0.853 0.713  1.19E−120 Apoc4  3.10E−122 −0.428496936 0.944 0.98  7.71E−118 Gnmt  7.88E−122 −0.46036106 0.972 0.988  1.96E−117 Cox4i1  8.25E−122 −0.454243631 0.904 0.958  2.05E−117 Ssr3  7.84E−120 0.521769281 0.765 0.596  1.95E−115 Glud1  1.95E−119 0.451048591 0.958 0.905  4.85E−115 P4hb  4.64E−119 0.405223744 0.973 0.941  1.15E−114 Itih3  4.97E−115 0.492908293 0.931 0.89  1.23E−110 Cyp4a10  1.47E−114 −0.742207081 0.322 0.657  3.66E−110 Saa2  5.09E−114 0.964488054 0.52 0.222  1.26E−109 Apcs  6.96E−112 0.606730845 0.738 0.525  1.73E−107 Creld2  1.82E−109 0.608652695 0.583 0.296  4.53E−105 Myh9  1.48E−108 0.6391137 0.595 0.318  3.67E−104 Tmem205  7.63E−107 −0.472107677 0.816 0.934  1.89E−102 Egfr  3.14E−106 0.504957782 0.882 0.809  7.81E−102 C8g  4.37E−106 −0.481964476 0.79 0.91  1.09E−101 Serpina1b  2.55E−105 −0.301770579 0.984 0.996  6.34E−101 Ces1d  9.18E−104 −0.428906017 0.797 0.923 2.28E−99 C3  1.35E−103 0.449521065 0.996 0.99 3.34E−99 Cyp8b1  4.96E−103 −0.553616206 0.489 0.745 1.23E−98 B2m  3.29E−102 −0.417973886 0.905 0.963 8.16E−98 Dnajc3  8.00E−101 0.45638751 0.85 0.772 1.99E−96 Eif4g2 8.04E−99 0.465990267 0.8 0.678 2.00E−94 Mup13 8.39E−99 −0.694889672 0.257 0.546 2.08E−94 Rnase4 1.83E−98 0.517836403 0.963 0.921 4.54E−94 Rps27l 2.39E−98 −0.548506218 0.658 0.849 5.93E−94 Iigp1 2.98E−97 0.454178892 0.832 0.759 7.41E−93 Gadd45g 3.17E−97 −0.614019025 0.311 0.639 7.86E−93 Eef1a1 4.27E−96 0.439251983 0.919 0.85 1.06E−91 Pdia4 5.79E−95 0.488166898 0.733 0.595 1.44E−90 Hnf4a 7.91E−95 0.454905579 0.85 0.743 1.96E−90 Arrdc3 1.26E−94 0.526871989 0.52 0.213 3.13E−90 Cyp2c29 9.40E−93 −0.586003377 0.709 0.93 2.33E−88 Cth 1.96E−92 −0.510899065 0.708 0.838 4.86E−88 Orm1 3.67E−90 0.365144434 0.963 0.952 9.11E−86 Actb 1.97E−88 0.38446276 0.919 0.886 4.90E−84 Hint1 4.47E−88 −0.473665273 0.691 0.858 1.11E−83 Serpina1e 8.25E−88 −0.284344569 0.993 0.999 2.05E−83 Pgrmc1 9.39E−88 0.350152674 0.953 0.94 2.33E−83 AI182371 1.18E−87 0.447854829 0.747 0.622 2.93E−83 Pzp 2.47E−87 0.41600896 0.984 0.986 6.13E−83 Oat 3.36E−87 −0.521209343 0.263 0.611 8.34E−83 Ces3a 3.37E−86 −0.36873562 0.884 0.967 8.38E−82 Calm1 3.86E−86 0.413146039 0.794 0.722 9.59E−82 Sod1 6.37E−86 −0.303629074 0.935 0.983 1.58E−81 Gm26917 2.48E−84 0.823736053 0.391 0.181 6.16E−80 Adh1 1.27E−83 −0.342018972 0.942 0.96 3.15E−79 Elovl2 6.28E−83 0.45224665 0.826 0.699 1.56E−78 Cox6c 1.19E−82 −0.502802751 0.724 0.884 2.96E−78 Pdcd4 2.20E−82 0.48815423 0.677 0.498 5.46E−78 Hmgcs2 6.68E−82 −0.317281221 0.951 0.986 1.66E−77 Atp5h 9.15E−82 −0.579498914 0.45 0.682 2.27E−77 Csad 1.94E−80 −0.531252493 0.469 0.744 4.82E−76 Manf 2.07E−80 0.468881688 0.632 0.44 5.14E−76 Ech1 2.78E−80 −0.429132615 0.715 0.856 6.90E−76 Ces1c 9.71E−80 −0.278292823 0.985 0.985 2.41E−75 Lrg1 1.78E−78 0.436838294 0.849 0.736 4.43E−74 Insig1 1.09E−76 0.465534816 0.626 0.426 2.72E−72 Steap4 1.33E−76 0.475973731 0.481 0.222 3.30E−72 Gm24270 1.88E−76 0.26796863 0.145 0.006 4.67E−72 Hc 3.46E−74 0.367935082 0.905 0.903 8.59E−70 Cyp2e1 9.55E−74 −0.499033632 0.688 0.911 2.37E−69 Nr1d2 2.65E−71 0.430636791 0.442 0.179 6.58E−67 1110008F13Rik 3.48E−71 −0.455270589 0.427 0.648 8.65E−67 Canx 6.16E−71 0.343383207 0.872 0.835 1.53E−66 Cfh 9.84E−71 0.400919606 0.921 0.897 2.44E−66 Ndufa4 2.17E−70 −0.443311137 0.766 0.889 5.38E−66 Cebpb 3.92E−70 −0.471579534 0.216 0.45 9.72E−66 Dhcr24 5.03E−70 0.423756767 0.857 0.783 1.25E−65 Ephx2 2.03E−69 −0.369303553 0.849 0.937 5.05E−65 Alas1 4.49E−69 −0.489837477 0.519 0.729 1.12E−64 Apoa5 1.45E−67 −0.298987336 0.924 0.974 3.60E−63 Selenbp2 3.48E−67 −0.383324562 0.868 0.937 8.65E−63 Kng1 4.27E−67 0.265777676 0.987 0.991 1.06E−62 Tram1 4.75E−67 0.411080257 0.7 0.512 1.18E−62 Saa4 3.40E−66 0.375528565 0.823 0.749 8.44E−62 C8b 7.20E−66 0.318703124 0.898 0.881 1.79E−61 mt-Nd6 1.13E−64 −0.477851134 0.294 0.577 2.81E−60 Ddt 1.25E−64 −0.422410948 0.64 0.829 3.10E−60 Cyp2c37 2.32E−64 −0.487522606 0.314 0.608 5.76E−60 Ugt2b36 2.41E−64 −0.329316239 0.875 0.93 5.98E−60 Cyp2a5 2.49E−64 −0.681077987 0.272 0.555 6.19E−60 Serpina3n 1.16E−63 0.413696164 0.719 0.574 2.88E−59 Hpd 7.70E−63 −0.313324027 0.952 0.976 1.91E−58 Inmt 2.34E−62 −0.44352952 0.831 0.884 5.81E−58 Cox6a1 7.81E−62 −0.366697192 0.746 0.887 1.94E−57 Spcs3 8.20E−62 0.394206972 0.483 0.283 2.04E−57 Serpina3c 9.00E−61 −0.408878947 0.198 0.385 2.23E−56 Acsl1 1.58E−60 −0.370316988 0.796 0.924 3.93E−56 Qsox1 3.27E−60 0.342352868 0.784 0.707 8.13E−56 Lrp1 4.30E−60 0.505128824 0.694 0.591 1.07E−55 Chchd2 2.26E−59 −0.394916772 0.801 0.916 5.60E−55 Hsd3b7 2.44E−59 −0.395256634 0.679 0.798 6.07E−55 Ndufb11 4.81E−59 −0.42752525 0.539 0.735 1.19E−54 Sparcl1 8.16E−59 −0.253616986 0 0.136 2.03E−54 Cltc 1.37E−58 0.438067775 0.61 0.414 3.40E−54 Cyp2d10 4.66E−58 −0.323151441 0.822 0.921 1.16E−53 Sc5d 6.09E−57 0.345016882 0.879 0.776 1.51E−52 Gjb2 4.40E−56 0.391136188 0.709 0.572 1.09E−51 Prg4 4.56E−56 0.430643187 0.421 0.188 1.13E−51 Rdx 5.22E−56 0.373557306 0.729 0.63 1.30E−51 Fos 6.68E−56 0.432003299 0.654 0.51 1.66E−51 Rdh7 1.03E−55 −0.269043262 0.932 0.969 2.55E−51 Dcxr 1.08E−55 −0.410666503 0.436 0.631 2.69E−51 C8a 1.48E−55 0.333650228 0.902 0.887 3.67E−51 Cpb2 2.27E−55 0.322179327 0.879 0.813 5.64E−51 Akr1c6 3.55E−55 −0.317638782 0.95 0.971 8.81E−51 Fndc3b 3.72E−55 0.348474602 0.291 0.096 9.25E−51 Cat 7.43E−55 0.262624418 0.978 0.971 1.84E−50 Clpx 9.40E−55 −0.404735614 0.635 0.783 2.33E−50 Uso1 9.63E−55 0.388069473 0.597 0.434 2.39E−50 Kmo 2.30E−54 0.302208311 0.778 0.732 5.72E−50 Rpn1 3.25E−54 0.41242919 0.605 0.444 8.06E−50 Hbb-bs 4.64E−54 1.042581651 0.145 0.018 1.15E−49 Tmed7 5.33E−54 0.386771014 0.563 0.367 1.32E−49 Gm4076 1.10E−53 −0.325469418 0.019 0.184 2.72E−49 Pdia6 1.15E−53 0.336506977 0.779 0.712 2.86E−49 Abca1 2.83E−53 0.439378423 0.556 0.377 7.04E−49 Hspa13 4.18E−53 0.354844877 0.404 0.192 1.04E−48 Cyb5r3 7.95E−53 0.339033056 0.8 0.725 1.97E−48 Ubc 9.16E−53 −0.370487607 0.742 0.872 2.28E−48 Apob 3.60E−52 0.4272457 0.983 0.989 8.94E−48 Pon1 5.27E−52 −0.322748466 0.829 0.906 1.31E−47 Slc7a2 9.89E−52 0.352564931 0.796 0.735 2.46E−47 Saa1 1.82E−51 0.558211954 0.792 0.662 4.53E−47 Nedd4 2.35E−51 0.377388355 0.647 0.524 5.84E−47 Mug2 3.08E−51 0.370406564 0.784 0.738 7.64E−47 AA474408 6.40E−51 0.43640813 0.278 0.094 1.59E−46 Cyp2c70 7.75E−51 0.336400438 0.89 0.834 1.92E−46 Cp 1.59E−50 0.317404056 0.947 0.943 3.96E−46 mt-Tq 3.53E−50 0.287889985 0.225 0.057 8.77E−46 Aadac 4.09E−50 −0.40376663 0.791 0.86 1.02E−45 Usp9x 1.24E−49 0.407617259 0.502 0.299 3.09E−45 Orm2 1.38E−49 0.271460545 0.285 0.09 3.43E−45 Igfbp2 4.52E−49 −0.345087789 0.768 0.885 1.12E−44 Hao1 7.16E−49 0.32303248 0.83 0.758 1.78E−44 Oaz1 8.48E−49 −0.374797984 0.594 0.75 2.11E−44 Cps1 9.93E−49 0.32450205 0.982 0.971 2.47E−44 Retsat 1.08E−48 −0.365840188 0.709 0.83 2.69E−44 Gm5096 1.55E−48 −0.363089147 0.287 0.468 3.85E−44 Gchfr 3.21E−48 −0.386867237 0.604 0.768 7.98E−44 Mup8 5.50E−48 −0.613334367 0.218 0.373 1.37E−43 Atp8b1 6.17E−48 0.362807422 0.391 0.182 1.53E−43 Zfp683 1.06E−47 −0.421395009 0.001 0.116 2.64E−43 Tmem30a 1.20E−47 0.332760453 0.766 0.664 2.98E−43 Cxcl1 1.29E−47 0.449766784 0.482 0.314 3.20E−43 Pten 1.30E−46 0.355902258 0.612 0.458 3.22E−42 mmu-mir-6236 1.50E−46 0.787474192 0.896 0.837 3.73E−42 Hspa8 1.60E−46 −0.359978165 0.58 0.756 3.96E−42 Hs3st3b1 2.33E−46 0.343007923 0.442 0.241 5.78E−42 Prkd3 2.71E−46 0.366517526 0.631 0.49 6.72E−42 Dnajc12 4.61E−46 0.322094554 0.275 0.108 1.15E−41 Etnppl 6.89E−46 −0.428291487 0.409 0.606 1.71E−41 Rsp14 9.86E−46 −0.292251029 0.815 0.917 2.45E−41 Hint2 1.17E−45 −0.37016853 0.51 0.676 2.90E−41 Mup20 1.28E−45 −0.281871664 0.988 1 3.18E−41 Snord118 3.42E−45 0.391412496 0.449 0.248 8.50E−41 Csde1 3.72E−45 0.326883793 0.687 0.577 9.23E−41 Adh4 1.11E−44 0.376928101 0.667 0.521 2.75E−40 Rps2 1.35E−44 −0.384454173 0.583 0.757 3.34E−40 Lpgat1 1.38E−44 0.394625955 0.635 0.502 3.42E−40 S100a1 1.97E−44 −0.376186192 0.494 0.661 4.89E−40 Acot1 2.09E−44 −0.286204152 0.059 0.237 5.19E−40 mt-Tm 2.31E−44 0.284684642 0.274 0.093 5.75E−40 Il13ra1 4.07E−44 0.30296595 0.33 0.143 1.01E−39 Rab1 8.74E−44 0.352627435 0.588 0.438 2.17E−39 Rrbp1 1.08E−43 0.306944991 0.823 0.768 2.68E−39 Khk 1.45E−43 −0.29761703 0.822 0.863 3.60E−39 Fabp2 1.67E−43 −0.39219613 0.437 0.622 4.14E−39 Efna1 2.79E−43 0.336097237 0.482 0.309 6.92E−39 Sds 5.49E−43 −0.407006722 0.443 0.67 1.36E−38 Ak3 8.39E−43 0.289040998 0.772 0.7 2.08E−38 Slc38a4 1.50E−42 0.263698621 0.897 0.877 3.73E−38 Slc3a1 1.55E−42 0.340997565 0.378 0.189 3.84E−38 Cmah 1.72E−42 0.361552447 0.607 0.465 4.27E−38 Sar1b 3.22E−42 −0.317607513 0.648 0.772 8.00E−38 Itih2 3.32E−42 0.298659728 0.922 0.884 8.24E−38 Acox1 3.87E−42 0.275171428 0.966 0.966 9.60E−38 Plg 4.24E−42 0.261736006 0.975 0.961 1.05E−37 Eef2 1.35E−41 0.270115373 0.89 0.873 3.35E−37 Trp53inp1 1.49E−41 0.367960906 0.473 0.308 3.70E−37 Cox7a2 1.23E−40 −0.363458039 0.638 0.784 3.06E−36 mt-Atp6 1.56E−40 −0.573743033 0.289 0.452 3.87E−36 Cfi 3.01E−40 0.251606433 0.914 0.905 7.48E−36 Eif4g1 4.16E−40 0.310782755 0.745 0.669 1.03E−35 Prdx1 5.51E−40 −0.267665106 0.839 0.927 1.37E−35 Atxn1 1.00E−39 0.304881734 0.311 0.137 2.49E−35 Ssr1 2.80E−39 0.327818552 0.523 0.339 6.95E−35 Etnk1 3.37E−39 0.352068809 0.49 0.328 8.38E−35 Ugt2a3 4.67E−39 −0.333441405 0.641 0.773 1.16E−34 Dstn 1.19E−38 0.324301394 0.57 0.37 2.95E−34 Mpc1 1.91E−38 −0.281762702 0.184 0.369 4.73E−34 Cyp2c54 2.08E−38 −0.326859698 0.566 0.759 5.16E−34 Nars 2.39E−38 0.353230364 0.593 0.471 5.94E−34 Gas5 3.41E−38 −0.336153154 0.337 0.527 8.46E−34 Ugt2b1 4.76E−38 −0.289461704 0.761 0.871 1.18E−33 Serp1 7.07E−38 0.312399212 0.809 0.721 1.76E−33 Mtus1 1.54E−37 0.362060296 0.563 0.42 3.83E−33 Cox5b 1.54E−37 −0.337825031 0.541 0.726 3.83E−33 Fdx1 1.76E−37 −0.344715083 0.482 0.625 4.37E−33 Igfbp1 2.33E−37 −0.316195447 0.519 0.717 5.79E−33 Ibtk 2.91E−37 0.331106132 0.43 0.247 7.23E−33 Fxyd1 3.75E−37 −0.311759144 0.547 0.721 9.32E−33 Slc41a2 3.84E−37 0.278262888 0.302 0.134 9.55E−33 Nab1 7.05E−37 0.33421071 0.491 0.315 1.75E−32 Hook1 8.56E−37 0.327423989 0.457 0.291 2.13E−32 Stard4 9.03E−37 0.351527506 0.559 0.399 2.24E−32 Usp4 9.90E−37 0.324732042 0.476 0.286 2.46E−32 Ndufb4 2.36E−36 −0.325145539 0.309 0.49 5.86E−32 Cml1 2.38E−36 −0.326909468 0.628 0.757 5.91E−32 Ndufs6 2.53E−36 −0.359160953 0.563 0.724 6.27E−32 Sec61a1 2.54E−36 0.313944633 0.607 0.476 6.31E−32 Arcn1 2.88E−36 0.327775216 0.53 0.366 7.15E−32 Nr5a2 3.30E−36 0.322039014 0.403 0.228 8.21E−32 Cyp2c50 3.34E−36 −0.290483498 0.739 0.888 8.29E−32 Aldh3a2 4.28E−36 −0.300776093 0.306 0.529 1.06E−31 BC025446 4.71E−36 0.29422883 0.486 0.306 1.17E−31 Cml2 4.99E−36 0.265441744 0.896 0.857 1.24E−31 Il6st 6.36E−36 0.333486533 0.448 0.273 1.58E−31 Ndufb2 9.30E−36 −0.341226284 0.468 0.629 2.31E−31 Lman1 9.78E−36 0.29860668 0.75 0.655 2.43E−31 Lrrc59 1.50E−35 0.318083941 0.449 0.28 3.72E−31 Mlec 2.35E−35 0.324558531 0.496 0.323 5.82E−31 Copa 3.03E−35 0.345094339 0.525 0.363 7.52E−31 Ipo7 4.40E−35 0.25915239 0.351 0.168 1.09E−30 Calu 4.76E−35 0.304112196 0.407 0.236 1.18E−30 Aox3 5.13E−35 0.287845433 0.916 0.894 1.27E−30 Acsl4 5.53E−35 0.314743242 0.478 0.323 1.37E−30 Sel1l 8.70E−35 0.33595882 0.544 0.392 2.16E−30 Ctsc 1.04E−34 0.300373343 0.336 0.271 2.58E−30 Cmbl 1.15E−34 −0.312422041 0.523 0.678 2.85E−30 Rps15 1.42E−34 −0.356137747 0.379 0.528 3.53E−30 Cald1 1.88E−34 0.258910981 0.79 0.749 4.66E−30 Atp5e 3.07E−34 −0.313641686 0.688 0.832 7.62E−30 Adck3 4.29E−34 −0.28251534 0.68 0.764 1.06E−29 Cyp4a14 4.45E−34 −0.372863761 0.245 0.431 1.10E−29 Cfhr2 5.63E−34 −0.321928662 0.814 0.868 1.40E−29 Ndufb6 6.93E−34 −0.306403298 0.636 0.759 1.72E−29 Uggt1 9.21E−34 0.284457726 0.385 0.204 2.29E−29 Rarres2 1.49E−33 −0.266616471 0.83 0.905 3.70E−29 Srpr 2.41E−33 0.305179041 0.532 0.387 5.97E−29 Id3 2.57E−33 −0.351088732 0.278 0.426 6.37E−29 Ndufa6 2.87E−33 −0.306815302 0.692 0.798 7.12E−29 Nop10 3.01E−33 −0.264928395 0.227 0.394 7.48E−29 Tob1 4.96E−33 0.312925608 0.565 0.43 1.23E−28 Nrp1 5.28E−33 0.334097753 0.426 0.253 1.31E−28 Vkorc1 5.36E−33 −0.297366597 0.38 0.54 1.33E−28 Stt3b 6.49E−33 0.319405267 0.485 0.335 1.61E−28 Trip12 6.80E−33 0.328304235 0.504 0.345 1.69E−28 Dnajb11 1.79E−32 0.315357308 0.557 0.43 4.44E−28 Gstp1 1.86E−32 −0.430197368 0.743 0.822 4.63E−28 Atp5f1 2.05E−32 −0.28724025 0.8 0.869 5.09E−28 Prdx4 3.84E−32 −0.307442113 0.47 0.607 9.54E−28 Ces3b 4.12E−32 −0.286685415 0.683 0.787 1.02E−27 Bzw1 4.22E−32 0.284147153 0.487 0.344 1.05E−27 Srp72 1.97E−31 0.310685136 0.597 0.461 4.90E−27 Ptprf 4.48E−31 0.307126385 0.588 0.464 1.11E−26 Ell2 4.71E−31 0.288090516 0.552 0.416 1.17E−26 Atp13a3 6.78E−31 0.303730845 0.546 0.41 1.68E−26 Ndufc2 7.73E−31 −0.308039389 0.465 0.579 1.92E−26 Pnpla7 8.71E−31 0.29608325 0.678 0.572 2.16E−26 Sco2 1.20E−30 −0.292870629 0.346 0.508 2.98E−26 Edem1 1.31E−30 0.286881059 0.566 0.429 3.26E−26 Akr1c19 1.49E−30 −0.272667086 0.389 0.527 3.70E−26 Slc39a14 1.88E−30 0.323040019 0.495 0.343 4.66E−26 Uqcr11 2.43E−30 −0.263241396 0.769 0.879 6.03E−26 Met 2.91E−30 0.288332662 0.434 0.274 7.22E−26 Man2a1 3.00E−30 0.28327895 0.675 0.583 7.46E−26 Lgr4 3.03E−30 0.268964381 0.399 0.226 7.52E−26 Rpl13 1.27E−29 −0.299693639 0.306 0.464 3.17E−25 Osbp19 1.49E−29 0.278773264 0.569 0.448 3.69E−25 Ctnnb1 2.29E−29 0.295681078 0.566 0.436 5.67E−25 Slc38a10 2.50E−29 0.285548034 0.449 0.291 6.20E−25 Arhgef12 2.67E−29 0.304679431 0.541 0.408 6.64E−25 Mtss1 2.84E−29 0.287581972 0.581 0.454 7.06E−25 Pik3c2a 9.21E−29 0.25938652 0.36 0.198 2.29E−24 Acly 1.12E−28 0.328803101 0.597 0.445 2.79E−24 Sc4mol 2.18E−28 −0.273479653 0.5 0.642 5.42E−24 Rplp1 2.38E−28 −0.286640389 0.597 0.757 5.92E−24 Arhgap5 2.81E−28 0.295235575 0.566 0.454 6.98E−24 Prdx5 2.81E−28 −0.260937182 0.731 0.834 6.99E−24 Zbtb20 4.95E−28 0.379090332 0.566 0.445 1.23E−23 Eprs 5.12E−28 0.301270543 0.587 0.488 1.27E−23 H6pd 5.18E−28 0.261357904 0.675 0.595 1.29E−23 Narf 7.05E−28 0.262933124 0.411 0.253 1.75E−23 Trib1 9.72E−28 0.287458438 0.455 0.308 2.41E−23 Esd 1.31E−27 −0.25379488 0.67 0.784 3.25E−23 Atp6v1f 1.33E−27 −0.252893521 0.244 0.403 3.29E−23 Grlf1 1.48E−27 0.295046691 0.413 0.257 3.69E−23 Bnip3 1.50E−27 −0.292803703 0.39 0.55 3.73E−23 Osbpl1a 1.54E−27 0.272788799 0.592 0.473 3.82E−23 Rps9 1.67E−27 −0.313951151 0.519 0.675 4.15E−23 Erp44 1.71E−27 0.279450299 0.469 0.336 4.24E−23 Tomm70a 1.75E−27 0.268786029 0.6 0.494 4.36E−23 Txndc5 1.86E−27 0.290124872 0.48 0.327 4.61E−23 Iqgap2 1.95E−27 0.254698841 0.748 0.677 4.85E−23 Arl5a 2.07E−27 0.264805346 0.459 0.289 5.13E−23 Cox7b 4.18E−27 −0.267397469 0.768 0.878 1.04E−22 Selenbp1 4.28E−27 −0.280021704 0.563 0.699 1.06E−22 Ftl1 4.31E−27 −0.349777423 0.27 0.409 1.07E−22 Lpin2 6.30E−27 0.277576437 0.7 0.597 1.56E−22 Magt1 6.93E−27 0.263295188 0.52 0.412 1.72E−22 Gm24245 1.17E−26 0.42420314 0.369 0.214 2.90E−22 Caprin1 1.32E−26 0.262825966 0.567 0.481 3.29E−22 Azin1 1.45E−26 0.270139699 0.46 0.322 3.60E−22 Fam120a 1.66E−26 0.280043634 0.51 0.391 4.13E−22 Atp11c 1.81E−26 0.260536506 0.649 0.587 4.49E−22 Surf4 2.20E−26 0.258577589 0.656 0.551 5.46E−22 Leap2 2.26E−26 −0.274778129 0.469 0.632 5.61E−22 Plin5 3.28E−26 −0.277759837 0.181 0.315 8.16E−22 Hspe1 3.41E−26 −0.290582957 0.413 0.557 8.48E−22 Copb2 3.61E−26 0.283928956 0.595 0.471 8.98E−22 Gm20594 4.38E−26 −0.360000649 0.204 0.294 1.09E−21 BC089597 1.29E−25 0.262237515 0.593 0.488 3.21E−21 Tmem243 1.37E−25 −0.26555147 0.407 0.557 3.41E−21 Eci1 1.76E−25 −0.276383144 0.581 0.709 4.37E−21 Cpne3 1.93E−25 0.258007443 0.456 0.31 4.78E−21 Cideb 1.94E−25 −0.27071201 0.557 0.676 4.82E−21 Gch1 2.96E−25 −0.282499843 0.502 0.643 7.35E−21 Dnajb9 3.65E−25 0.25864192 0.373 0.241 9.07E−21 Dennd5b 3.78E−25 0.293458876 0.476 0.334 9.38E−21 Srebf1 5.27E−25 0.27619787 0.439 0.307 1.31E−20 Ide 5.87E−25 0.251691529 0.604 0.494 1.46E−20 Kpnb1 9.41E−25 0.280415627 0.447 0.311 2.34E−20 Nr1i3 1.39E−24 −0.282083592 0.237 0.377 3.46E−20 Xiap 1.94E−24 0.26016306 0.504 0.378 4.81E−20 Nadk2 3.06E−24 0.257852312 0.539 0.417 7.60E−20 Proz 3.97E−24 0.263204472 0.622 0.53 9.85E−20 Prkaa2 4.37E−24 0.263640766 0.451 0.315 1.09E−19 Stat3 4.97E−24 0.297428438 0.459 0.318 1.23E−19 Ostc 5.87E−24 0.265829876 0.514 0.357 1.46E−19 Ireb2 6.99E−24 0.265741209 0.469 0.321 1.74E−19 Mt1 7.07E−24 −0.348193009 0.41 0.556 1.76E−19 Sec31a 7.08E−24 0.263042758 0.462 0.31 1.76E−19 Brd2 2.14E−23 0.266388486 0.512 0.408 5.30E−19 Fcgrt 2.28E−23 −0.269314211 0.461 0.599 5.65E−19 Gpam 6.56E−23 0.250377871 0.329 0.199 1.63E−18 Cyp27a1 9.47E−23 −0.251578373 0.759 0.837 2.35E−18 Erbb2ip 1.42E−22 0.279650574 0.482 0.364 3.54E−18 Ranbp2 2.50E−22 0.26594209 0.484 0.338 6.20E−18 Raf13 3.68E−22 0.255296715 0.612 0.516 9.13E−18 Txnrd1 5.19E−22 0.260866185 0.564 0.441 1.29E−17 Mbnl1 6.12E−22 0.25020478 0.428 0.297 1.52E−17 Jak1 8.54E−22 0.254122657 0.482 0.342 2.12E−17 Psme4 9.89E−22 0.262584214 0.58 0.478 2.46E−17 Golga4 2.75E−21 0.271769698 0.447 0.31 6.83E−17 Ehhadh 6.02E−21 −0.250472633 0.552 0.691 1.49E−16 Lasp1 7.14E−21 0.253021439 0.361 0.243 1.77E−16 Rpl32 9.18E−21 −0.254910119 0.636 0.757 2.28E−16 Copz1 1.57E−20 0.257722711 0.501 0.385 3.89E−16 Eif4b 2.82E−20 0.255987641 0.542 0.438 6.99E−16 Gm23935 3.29E−20 0.721300311 0.919 0.925 8.16E−16 Ddost 4.03E−20 0.250356033 0.493 0.392 1.00E−15 Fasn 5.17E−20 0.291406736 0.449 0.345 1.28E−15 Sh3bgrl 5.20E−20 0.25128227 0.512 0.385 1.29E−15 Macf1 1.18E−19 0.261666188 0.349 0.219 2.94E−15 Deptor 2.26E−19 0.260618372 0.583 0.473 5.60E−15 Prox1 2.48E−19 0.266329524 0.477 0.351 6.16E−15 Sbno1 2.55E−19 0.250529348 0.36 0.228 6.33E−15 Atp1a1 5.55E−19 0.270031448 0.532 0.457 1.38E−14 Ubb 1.44E−17 −0.259339434 0.329 0.45 3.57E−13 Gstm3 4.48E−16 −0.318590137 0.293 0.414 1.11E−11 Por 3.09E−13 −0.271635533 0.589 0.675 7.68E−09 Mup2 1.04E−11 −0.274243623 0.364 0.392 2.59E−07 Mup1 0.000864034 −0.261837735 0.588 0.583 1

TABLE 4a Differentially expressed genes between time point A48 and untreated (UT) p_val avg_logFC pct.1 pct.2 p_val_adj Cyp4a14 0 1.78777169 0.991 0.431 0 Cyp4a10 0 1.14855488 0.991 0.657 0 Mat1a 0 1.05694824 1 0.966 0 Hmgcs2 0 0.782364 1 0.986 0 Mup11 0 −1.6799694 0.896 1 0 Mup18 0 −1.9532293 0.887 0.997 0 Mup6 0 −2.0417075 0.885 0.992 0 Mup9 0 −2.0539847 0.589 0.976 0 Mup17 0 −2.3251338 0.962 1 0 Mup19 0 −2.5024654 0.938 1 0 mt-Nd2  5.70E−292 −1.0887684 0.995 0.999  1.42E−287 mt-Co1  1.02E−291 −1.2589436 0.995 0.999  2.52E−287 Mfsd2a  3.98E−286 0.78121324 0.731 0.148  9.87E−282 Angpt13  1.31E−281 0.7223486 0.995 0.944  3.25E−277 Apoc2  2.70E−279 0.96935076 0.98 0.802  6.70E−275 Ces1c  2.09E−273 0.55433171 0.999 0.985  5.20E−269 Selenbp2  4.62E−273 −1.1339606 0.807 0.937  1.15E−268 Chchd10  4.58E−272 0.81121599 0.995 0.944  1.14E−267 Mup7  5.30E−265 −1.0899502 0.93 0.998  1.32E−260 Apoe  1.09E−264 0.47353426 1 1  2.72E−260 mt-Nd4  3.35E−263 −1.0213393 0.997 0.998  8.31E−259 mt-Cytb  1.81E−254 −1.0028016 0.996 0.999  4.51E−250 mt-Rnr2  3.30E−250 −0.8153022 1 1  8.18E−246 mt-Nd5  1.44E−247 −1.0547847 0.988 0.995  3.56E−243 Retsat  6.60E−238 0.79666675 0.988 0.83  1.64E−233 Mup16  2.03E−236 −1.084786 0.715 0.934  5.04E−232 Apoh  2.06E−234 0.46628252 0.998 0.986  5.13E−230 Mup21  2.18E−228 −1.0729318 0.777 0.929  5.42E−224 Ahsg  1.32E−226 0.36968503 1 1  3.27E−222 Abcd2  1.26E−222 0.32535888 0.473 0.052  3.13E−218 Aldob  4.71E−217 0.49713861 1 0.996  1.17E−212 Rgs16  1.46E−216 0.48956756 0.601 0.113  3.62E−212 Ttc36  4.07E−214 0.52379567 0.996 0.95  1.01E−209 Dbp  1.96E−213 0.28461585 0.52 0.07  4.86E−209 Slco1a4  4.08E−213 0.62444908 0.77 0.238  1.01E−208 Agt  4.67E−213 0.63305205 0.981 0.817  1.16E−208 Herpud1  7.00E−209 0.65043654 0.985 0.803  1.74E−204 Hrg  1.97E−205 0.60700462 0.987 0.831  4.88E−201 Gc  4.59E−200 0.34083171 1 0.999  1.14E−195 Cp  4.65E−198 0.55546665 0.995 0.943  1.15E−193 Slc25a47  3.79E−196 0.66741013 0.992 0.927  9.42E−192 mt-Nd1  3.99E−196 −0.5982047 1 1  9.90E−192 Vtn  1.22E−195 0.50147723 1 0.983  3.02E−191 F2  3.37E−193 0.42280245 0.999 0.969  8.36E−189 Gm13775  1.59E−192 −1.1035721 0.321 0.761  3.94E−188 Snord118  1.79E−192 0.65098072 0.766 0.248  4.45E−188 mt-Rnr1  1.01E−191 −0.6354582 1 1  2.51E−187 Reep6  1.19E−191 0.66052002 0.967 0.794  2.95E−187 Tef  1.43E−190 0.37649582 0.651 0.148  3.55E−186 Ttpa  3.04E−190 0.57816408 0.991 0.869  7.56E−186 St3gal5  7.03E−187 0.66332104 0.914 0.49  1.75E−182 Sepp1  2.92E−186 0.38687237 1 1  7.25E−182 Serping1  1.89E−182 0.5901636 0.987 0.87  4.70E−178 Decr1  2.76E−180 0.57780557 0.96 0.694  6.84E−176 Gm23935  2.81E−179 0.70920114 0.997 0.925  6.98E−175 Ndrg2  9.21E−178 0.43980324 1 0.939  2.29E−173 Sult1a1  8.15E−177 0.59346826 0.963 0.707  2.02E−172 Mup4  1.14E−176 −1.2590554 0.78 0.898  2.84E−172 Apoa5  1.06E−175 0.42466196 0.998 0.974  2.63E−171 Mup5  8.55E−175 −1.4352143 0.655 0.839  2.12E−170 Rbp4  2.98E−170 0.38026101 1 0.999  7.41E−166 Rdh7  2.87E−169 0.4431568 0.996 0.969  7.14E−165 Serpina3m  7.11E−164 0.58543579 0.949 0.722  1.77E−159 Nudt7  1.70E−162 −1.1432695 0.738 0.83  4.22E−158 Fth1  1.20E−161 0.42544729 0.996 0.978  2.98E−157 Gm6484  1.57E−161 0.43191488 0.627 0.174  3.91E−157 Ttr  4.92E−161 0.42565826 1 1  1.22E−156 Grn  2.23E−159 0.55458402 0.844 0.396  5.54E−155 Pabpc1  2.53E−159 0.59469924 0.912 0.592  6.28E−155 Fkbp5  2.41E−156 0.31305366 0.54 0.117  5.98E−152 Cdo1  4.87E−154 0.46952727 0.997 0.96  1.21E−149 Lcat  2.30E−152 0.52223232 0.973 0.781  5.72E−148 Car3  2.49E−152 −0.6790672 0.957 0.974  6.19E−148 Syvn1  2.49E−150 0.34196184 0.603 0.165  6.18E−146 Oaf  6.13E−146 0.52764092 0.969 0.794  1.52E−141 Plin5  4.86E−145 0.42261205 0.788 0.315  1.21E−140 Cyp17a1  2.78E−143 0.25634278 0.338 0.044  6.90E−139 Mup15  3.34E−143 −1.2816696 0.209 0.617  8.29E−139 Apoa4  7.77E−143 0.74347161 0.778 0.339  1.93E−138 P4hb  1.09E−142 0.38448979 0.995 0.941  2.70E−138 Igfbp4  6.65E−142 0.4496666 0.99 0.866  1.65E−137 Ambp  7.17E−142 0.31533589 1 0.993  1.78E−137 Elovl3  1.16E−140 −0.8184539 0.669 0.827  2.87E−136 Rpl38  2.08E−140 0.32217952 0.596 0.16  5.16E−136 Hmgcl  8.90E−140 0.57017343 0.956 0.729  2.21E−135 Abcb4  1.10E−139 0.51123675 0.956 0.675  2.74E−135 Hp  4.14E−136 0.30554085 1 0.999  1.03E−131 Ildr2  4.96E−136 0.28219186 0.588 0.159  1.23E−131 Ube2r2  3.18E−135 0.50268344 0.884 0.525  7.90E−131 Bfar  7.09E−135 0.34808175 0.742 0.27  1.76E−130 Cyp2a12  3.08E−133 0.49599281 0.981 0.884  7.65E−129 Wbp1l  7.93E−131 0.51781333 0.91 0.606  1.97E−126 Hsd17b13  2.60E−130 0.74833751 0.934 0.74  6.45E−126 Slc35g1  4.66E−130 0.25441963 0.521 0.133  1.16E−125 Serpina3n  4.85E−130 0.51010138 0.902 0.574  1.20E−125 Mup3  7.70E−130 −0.3534779 1 1  1.91E−125 Apoc3  2.95E−129 0.35021276 1 0.993  7.33E−125 mt-Co2  8.06E−129 −0.8270395 0.14 0.629  2.00E−124 Prodh2  2.15E−128 0.49365697 0.918 0.611  5.34E−124 Aldh9a1  3.44E−128 0.46052647 0.964 0.763  8.53E−124 F10  1.60E−127 0.41275991 0.989 0.895  3.97E−123 Tmbim6  2.08E−127 0.40188954 0.996 0.942  5.16E−123 Ces1b  2.43E−126 0.49918312 0.838 0.437  6.03E−122 Akr1c6  2.52E−126 −0.5780467 0.955 0.971  6.27E−122 Lpin1  2.69E−126 0.52324678 0.736 0.31  6.67E−122 Sh3glb1  5.75E−126 0.38610114 0.695 0.258  1.43E−121 Slc27a5  6.41E−125 0.40331028 0.987 0.893  1.59E−120 Vnn3  8.41E−125 0.33728247 0.684 0.241  2.09E−120 Pnpla2  2.09E−123 0.3417335 0.687 0.247  5.18E−119 Lims2  5.53E−121 0.36535639 0.679 0.249  1.37E−116 Ppara  1.26E−120 0.40400248 0.831 0.407  3.13E−116 Gys2  3.37E−120 0.43932352 0.784 0.358  8.36E−116 Cyp3a25  4.59E−120 0.35070342 0.995 0.919  1.14E−115 Nr1i3  3.28E−119 0.47025715 0.814 0.377  8.14E−115 Decr2  1.73E−118 0.45805699 0.92 0.634  4.30E−114 Atp5b  2.24E−118 0.34893252 0.997 0.942  5.56E−114 Cox8a  4.00E−118 0.54660995 0.89 0.621  9.92E−114 Gm2a  4.51E−118 0.43890359 0.827 0.427  1.12E−113 Atp5h  7.92E−118 0.53194908 0.933 0.682  1.97E−113 Acad11  1.10E−117 0.4378614 0.896 0.564  2.74E−113 Ephx2  1.34E−117 0.3598736 0.993 0.937  3.32E−113 Hspa5  3.19E−117 0.40850657 0.991 0.944  7.93E−113 Scand1  4.17E−117 0.25755493 0.579 0.174  1.04E−112 Sdhc  2.61E−116 0.45765895 0.91 0.63  6.47E−112 Slc25a20  4.35E−115 0.4293254 0.877 0.498  1.08E−110 Uroc1  7.32E−115 0.50396621 0.914 0.615  1.82E−110 Amy1  1.28E−114 0.44291653 0.943 0.676  3.19E−110 Mlycd  3.29E−114 0.43192633 0.893 0.503  8.18E−110 Slc27a2  4.49E−114 0.37825624 0.996 0.949  1.12E−109 Gstt3  5.33E−114 0.36201954 0.737 0.286  1.32E−109 Gyk  4.07E−113 0.37405715 0.778 0.35  1.01E−108 Cox5a  6.86E−113 0.45488054 0.938 0.702  1.70E−108 Ugt2b5  2.21E−111 0.33506188 0.996 0.959  5.49E−107 Mgll  3.59E−111 0.40884648 0.844 0.449  8.92E−107 Khk  5.46E−111 0.4591056 0.982 0.863  1.36E−106 Rpl4  1.15E−110 0.3674266 0.987 0.915  2.85E−106 Fah  4.69E−109 0.39558346 0.974 0.834  1.17E−104 Echs1  7.81E−109 0.45110855 0.971 0.817  1.94E−104 Brap  1.53E−108 0.38180614 0.829 0.427  3.80E−104 Hdac11  4.53E−108 0.32069886 0.713 0.285  1.13E−103 Bnip3  1.03E−107 0.45283659 0.876 0.55  2.56E−103 Slc40a1  1.04E−107 0.3734929 0.744 0.328  2.58E−103 Ddb1  2.29E−107 0.39083919 0.83 0.428  5.69E−103 Inhbc  4.12E−107 0.25374724 0.595 0.201  1.02E−102 Armc1  2.37E−106 0.26734554 0.632 0.225  5.88E−102 Scp2  2.42E−106 −0.4139053 0.995 0.986  6.01E−102 Mup12  2.57E−106 −0.7129524 0.754 0.86  6.39E−102 Camk2n1  1.71E−105 0.30984563 0.691 0.278  4.25E−101 Lpin2  2.11E−105 0.46846516 0.921 0.597  5.23E−101 Saa1  3.09E−105 −1.0130216 0.393 0.662  7.67E−101 Acat1  3.61E−105 0.38666145 0.978 0.838  8.97E−101 Sfxn2  4.28E−105 0.27640229 0.654 0.243  1.06E−100 Slc25a10  1.78E−104 0.41888519 0.877 0.536  4.43E−100 Snord13  2.03E−104 0.25675581 0.559 0.175  5.04E−100 mt-Co3  3.45E−104 −0.8113661 0.213 0.603  8.56E−100 Pigr  1.34E−103 0.47648784 0.977 0.947 3.33E−99 Hspa8  2.84E−103 0.41559393 0.952 0.756 7.06E−99 Tmbim4  4.95E−103 0.38382176 0.784 0.394 1.23E−98 Agpat6  1.27E−102 0.38404305 0.884 0.517 3.14E−98 Ppp2r5e  3.79E−102 0.29726616 0.662 0.259 9.40E−98 Serpina1e  9.56E−102 −0.3734273 0.998 0.999 2.37E−97 Gltscr2  1.21E−101 0.34501105 0.83 0.424 3.00E−97 Atp5k  6.53E−101 0.41069121 0.935 0.678 1.62E−96 Klf9  1.72E−100 0.38955613 0.862 0.52 4.28E−96 Tcea3  1.98E−100 0.40437799 0.825 0.439 4.93E−96 Ass1  3.83E−100 −0.4198124 0.978 0.962 9.51E−96 Prdx1  4.65E−100 −0.4756182 0.937 0.927 1.15E−95 Kng1  6.40E−100 0.25435632 0.999 0.991 1.59E−95 Slc37a4  7.88E−100 0.41531041 0.858 0.502 1.96E−95 Ctsh 9.91E−99 0.43587811 0.945 0.727 2.46E−94 Serpinf1 4.39E−98 0.37187623 0.976 0.864 1.09E−93 Yipf3 8.87E−98 0.29415639 0.68 0.275 2.20E−93 Lipa 1.27E−97 0.4009047 0.904 0.61 3.16E−93 Azgp1 1.30E−97 0.27232649 0.997 0.968 3.22E−93 Hsd3b5 1.31E−97 −0.8595063 0.301 0.587 3.26E−93 D17Wsu92e 3.43E−96 0.38410204 0.909 0.588 8.53E−92 Abhd14b 3.92E−96 0.39606641 0.885 0.565 9.72E−92 C4b 4.24E−96 0.41301977 0.975 0.883 1.05E−91 Zfp91 1.40E−95 0.36762155 0.855 0.492 3.48E−91 Gfra1 2.52E−95 0.37425606 0.867 0.498 6.26E−91 0610005C13Rik 2.86E−95 0.38034455 0.944 0.653 7.11E−91 Tm4sf4 1.44E−94 0.2596724 0.658 0.256 3.56E−90 Smoc1 1.84E−94 0.26326942 0.626 0.238 4.56E−90 Sec14l2 1.15E−93 0.36294512 0.98 0.856 2.85E−89 F12 1.52E−93 0.37294854 0.966 0.814 3.77E−89 Pitpnb 1.52E−93 0.34010954 0.795 0.393 3.78E−89 BC025446 1.65E−93 0.30101942 0.714 0.306 4.10E−89 Acot12 2.15E−93 0.31850968 0.825 0.425 5.33E−89 Tgoln1 3.18E−93 0.39559469 0.891 0.575 7.90E−89 Arhgap5 1.96E−92 0.34695663 0.852 0.454 4.86E−88 Fcgrt 3.70E−92 0.36904045 0.91 0.599 9.20E−88 Fabp1 6.83E−92 −0.3049262 0.999 1 1.70E−87 Eci2 2.39E−91 0.36362519 0.944 0.698 5.93E−87 Sec61a1 2.87E−91 0.3812213 0.825 0.476 7.12E−87 Aco2 6.42E−91 0.3485193 0.846 0.493 1.59E−86 Cdip1 3.73E−90 0.25310032 0.674 0.273 9.26E−86 Ctsa 3.79E−90 0.30415135 0.731 0.33 9.41E−86 Etnppl 5.20E−90 0.57021741 0.866 0.606 1.29E−85 Lrg1 1.16E−89 0.39241541 0.945 0.736 2.88E−85 Abca6 1.96E−89 0.37574506 0.849 0.507 4.87E−85 Aldoa 3.68E−89 0.2857358 0.719 0.316 9.15E−85 Gabarap 4.31E−89 0.37626669 0.956 0.769 1.07E−84 Pbld1 1.46E−88 0.35826568 0.881 0.565 3.64E−84 Mia3 9.36E−88 0.37197189 0.91 0.61 2.33E−83 Sfxn1 3.26E−87 0.41219077 0.822 0.496 8.09E−83 Cyp1a2 1.61E−86 −0.6807537 0.567 0.794 4.00E−82 Ifnar2 1.94E−86 0.2837916 0.731 0.328 4.81E−82 Acadl 9.49E−86 0.33585482 0.916 0.612 2.36E−81 Serinc3 1.50E−85 0.34287593 0.793 0.433 3.73E−81 Apoc1 1.95E−85 0.28437006 1 0.999 4.84E−81 Cyp2c44 3.72E−85 0.43648833 0.924 0.698 9.23E−81 Actn4 9.93E−85 0.33312677 0.789 0.425 2.47E−80 Asgr2 1.03E−84 0.3550777 0.879 0.555 2.56E−80 Abcc3 1.65E−84 0.39254854 0.859 0.542 4.10E−80 Atf5 2.70E−84 0.3780825 0.909 0.641 6.70E−80 Tmem219 3.14E−84 0.26964524 0.664 0.28 7.80E−80 Hpx 3.75E−84 0.3181157 0.999 0.997 9.32E−80 G0s2 7.32E−84 0.39032412 0.692 0.33 1.82E−79 Shmt1 1.69E−83 0.35115019 0.882 0.556 4.20E−79 Mrpl43 1.78E−83 0.26402895 0.714 0.316 4.42E−79 Ggnbp2 1.97E−83 0.31843548 0.818 0.43 4.89E−79 Cyp2d26 3.17E−83 0.31789903 0.982 0.903 7.88E−79 Acbd5 3.49E−83 0.34046005 0.943 0.708 8.65E−79 Atxn7l3b 3.75E−83 0.32661693 0.846 0.476 9.30E−79 Cab39l 3.82E−83 0.26219157 0.733 0.331 9.50E−79 Mtdh 7.86E−83 0.28994736 0.819 0.428 1.95E−78 Creb3l3 7.93E−83 0.3329936 0.971 0.831 1.97E−78 Slc10a1 1.05E−82 0.37161916 0.984 0.843 2.61E−78 Ech1 2.53E−82 0.35576676 0.98 0.856 6.29E−78 Furin 3.12E−82 0.3476705 0.781 0.417 7.75E−78 Cpt2 7.06E−82 0.3131465 0.807 0.436 1.75E−77 Ctsd 8.31E−82 0.35186323 0.916 0.656 2.06E−77 Asl 2.52E−81 0.45960679 0.953 0.787 6.25E−77 Lamp1 6.63E−81 0.33067129 0.982 0.885 1.65E−76 Slc2a2 6.96E−81 0.37119647 0.824 0.479 1.73E−76 Gpld1 5.01E−80 0.34918584 0.877 0.577 1.24E−75 Bche 1.32E−79 0.29962103 0.752 0.369 3.27E−75 Gcdh 2.44E−79 0.31260712 0.977 0.85 6.06E−75 Dhcr24 2.63E−79 0.38999534 0.953 0.783 6.54E−75 Maob 2.50E−78 0.36130489 0.889 0.575 6.21E−74 Mttp 3.08E−78 0.34245511 0.933 0.697 7.64E−74 Clu 4.53E−78 0.26617797 0.997 0.958 1.12E−73 Cox6a1 8.00E−78 0.32671096 0.987 0.887 1.99E−73 Surf4 2.41E−77 0.32708715 0.873 0.551 5.98E−73 Suds3 4.51E−77 0.27997975 0.74 0.364 1.12E−72 Igf1 1.75E−76 0.34278741 0.985 0.904 4.34E−72 Phlda1 2.53E−76 0.30670303 0.72 0.356 6.29E−72 Akr1d1 6.54E−76 0.34507376 0.852 0.515 1.62E−71 Snx3 8.85E−76 0.26415091 0.693 0.324 2.20E−71 Pcbp2 9.01E−76 0.30951078 0.778 0.438 2.24E−71 Slc4a4 2.41E−75 0.26414508 0.708 0.336 5.99E−71 Tmed5 2.77E−75 0.31719235 0.86 0.492 6.87E−71 Hgfac 2.82E−75 0.30206409 0.786 0.438 7.00E−71 1600002H07Rik 4.78E−75 0.26043978 0.736 0.367 1.19E−70 Atp1a1 6.00E−75 0.31879405 0.8 0.457 1.49E−70 Aspdh 9.40E−75 0.29976949 0.776 0.411 2.34E−70 Atp2a2 9.70E−75 0.34965213 0.805 0.495 2.41E−70 Ivns1abp 5.96E−74 0.25484425 0.685 0.315 1.48E−69 Ubxn4 2.33E−73 0.31590951 0.893 0.579 5.79E−69 Pcx 3.13E−73 0.33904029 0.912 0.661 7.78E−69 Acadvl 4.86E−73 0.30727305 0.959 0.783 1.21E−68 Hnf4a 6.29E−73 0.34260828 0.94 0.743 1.56E−68 Pbld2 7.71E−73 0.30880678 0.891 0.586 1.91E−68 Slc25a13 2.11E−72 0.3099101 0.924 0.655 5.25E−68 Ahcy 2.94E−72 0.25978038 0.988 0.916 7.30E−68 Oplah 3.87E−72 0.30158653 0.805 0.455 9.61E−68 Cebpb 4.19E−72 0.29703786 0.815 0.45 1.04E−67 Sord 8.74E−72 0.31435807 0.987 0.931 2.17E−67 Eific 9.45E−72 0.29343555 0.868 0.541 2.35E−67 Pck1 1.11E−71 0.35910816 0.999 0.987 2.76E−67 Park7 5.64E−71 0.33535943 0.953 0.784 1.40E−66 Lifr 9.77E−71 −0.6366246 0.673 0.694 2.43E−66 Npc2 1.08E−70 0.25651649 0.767 0.397 2.69E−66 C130074G19Rik 1.40E−70 0.27256617 0.803 0.439 3.48E−66 Sdhd 1.50E−70 0.40776118 0.891 0.677 3.73E−66 Ctage5 1.61E−70 0.33481901 0.941 0.683 4.00E−66 Atp5g3 5.36E−70 0.30300905 0.985 0.911 1.33E−65 Man2a1 6.00E−70 0.33303555 0.856 0.583 1.49E−65 Man2b1 6.86E−70 0.25308423 0.691 0.327 1.70E−65 Atp5d 7.13E−70 0.3074367 0.935 0.712 1.77E−65 Hsd17b10 7.55E−70 0.40597546 0.927 0.7 1.87E−65 Sult1d1 1.68E−69 0.47541266 0.936 0.684 4.17E−65 Cpt1a 1.92E−69 0.3717929 0.896 0.651 4.77E−65 Scrpinf2 2.02E−69 0.3073114 0.966 0.843 5.01E−65 Map2k2 2.13E−69 0.28116858 0.832 0.505 5.29E−65 Cyp3a11 7.95E−69 0.35751032 1 1 1.97E−64 Galk1 7.57E−68 0.25083271 0.718 0.353 1.88E−63 Os9 7.80E−68 0.3000957 0.911 0.663 1.94E−63 Stbd1 2.40E−67 0.25163985 0.725 0.362 5.97E−63 Eef1d 7.21E−67 0.25178984 0.795 0.431 1.79E−62 Creg1 7.28E−67 0.29261497 0.993 0.926 1.81E−62 Itih1 8.18E−67 0.31889271 0.974 0.816 2.03E−62 Pnpla8 1.55E−66 0.28423148 0.875 0.544 3.85E−62 Hadh 1.60E−66 0.31148521 0.908 0.642 3.97E−62 2810007J24Rik 1.91E−66 −0.3323662 0.971 0.943 4.75E−62 Cyp2c70 4.18E−66 −0.5119271 0.887 0.834 1.04E−61 Mup8 5.86E−66 −0.8035587 0.099 0.373 1.45E−61 Cyp7b1 8.93E−66 −0.5490083 0.745 0.757 2.22E−61 C3 1.24E−65 0.25701603 1 0.99 3.07E−61 Etfb 4.53E−65 0.26087717 0.996 0.94 1.12E−60 Ninj1 8.63E−65 0.33268814 0.874 0.6 2.14E−60 Eif5 2.27E−64 0.29265666 0.953 0.74 5.63E−60 Pglyrp2 2.64E−64 0.28472176 0.754 0.414 6.57E−60 St13 2.78E−64 0.27490607 0.902 0.605 6.91E−60 BC089597 3.62E−64 0.32040389 0.813 0.488 9.00E−60 F9 7.60E−64 0.28721732 0.897 0.632 1.89E−59 Upb1 1.23E−63 0.30883423 0.945 0.759 3.05E−59 Dnajc3 1.92E−63 0.27870056 0.96 0.772 4.77E−59 Tomm70a 2.60E−63 0.26465337 0.84 0.494 6.45E−59 Hadha 7.87E−63 0.30184069 0.943 0.744 1.95E−58 Cfi 8.49E−63 0.27302279 0.984 0.905 2.11E−58 Gstp1 1.03E−62 −0.7039865 0.816 0.822 2.56E−58 Nfe211 1.25E−62 0.25237576 0.648 0.303 3.11E−58 Pccb 1.80E−62 0.28471305 0.901 0.644 4.48E−58 Cd1d1 2.74E−62 0.31029654 0.887 0.612 6.80E−58 Sec62 5.58E−62 0.25355237 0.891 0.582 1.38E−57 Ndufb10 1.58E−61 0.3124426 0.907 0.681 3.92E−57 Fam195a 3.67E−61 0.25895675 0.726 0.373 9.11E−57 Agpat3 4.91E−61 0.28331345 0.874 0.606 1.22E−56 Usmg5 5.77E−61 0.34205598 0.755 0.43 1.43E−56 Pla2g12b 1.63E−60 0.26759045 0.798 0.463 4.05E−56 Pim3 1.69E−60 0.28844058 0.845 0.537 4.19E−56 Rdx 2.64E−60 0.27239982 0.918 0.63 6.57E−56 Itih4 4.78E−60 0.25619887 0.989 0.948 1.19E−55 Aplp2 5.59E−60 0.29614531 0.89 0.625 1.39E−55 Tmem176b 6.55E−60 0.2869571 0.89 0.632 1.63E−55 Mst1 2.99E−59 0.26762035 0.81 0.491 7.42E−55 Pipox 3.78E−59 0.27664192 0.849 0.549 9.39E−55 Hal 8.00E−59 0.41089477 0.908 0.749 1.99E−54 1-Mar 9.16E−59 0.26809923 0.984 0.885 2.28E−54 C9 3.01E−58 −0.3557254 0.958 0.938 7.47E−54 Apoc4 3.29E−58 0.31784645 0.998 0.98 8.16E−54 Lman1 2.98E−57 0.29104793 0.908 0.655 7.40E−53 Slc7a2 7.19E−57 0.38667853 0.921 0.735 1.78E−52 Gsto1 2.33E−56 0.29242538 0.818 0.52 5.79E−52 Por 4.50E−56 0.33065864 0.921 0.675 1.12E−51 Fmo5 4.62E−56 0.25685221 0.979 0.837 1.15E−51 Slc25a39 1.37E−55 0.28667795 0.938 0.775 3.41E−51 Eef2 3.32E−55 0.2761614 0.976 0.873 8.24E−51 Ces2e 3.94E−55 0.26453598 0.852 0.535 9.79E−51 Mup14 5.64E−55 −0.7319112 0.458 0.616 1.40E−50 Tmem56 6.78E−55 0.27132827 0.878 0.612 1.68E−50 Atp5j 2.12E−54 0.31656359 0.916 0.757 5.27E−50 Glrx5 2.30E−54 0.26880807 0.886 0.588 5.72E−50 Dmgdh 4.17E−54 0.26793926 0.952 0.764 1.04E−49 Hsbp1 6.41E−54 0.25010647 0.792 0.498 1.59E−49 Hsd17b4 1.05E−53 0.26350655 0.971 0.818 2.60E−49 Sardh 2.77E−53 0.29292716 0.959 0.838 6.87E−49 Rgn 3.35E−53 −0.4023915 0.745 0.874 8.33E−49 Rxra 3.40E−53 0.26022884 0.849 0.574 8.43E−49 Ugp2 5.36E−53 0.30081989 0.945 0.749 1.33E−48 Fn1 4.88E−52 0.31062863 0.945 0.821 1.21E−47 Hsd3b7 7.74E−52 −0.4335194 0.82 0.798 1.92E−47 Comt 9.63E−52 −0.3017516 0.958 0.931 2.39E−47 Chpt1 1.19E−51 0.2736267 0.912 0.664 2.96E−47 Itih3 1.29E−51 0.2835814 0.978 0.89 3.20E−47 Cyp2d22 1.40E−51 0.25806171 0.835 0.546 3.48E−47 Gpt 3.62E−51 0.25721554 0.94 0.753 8.98E−47 Sds 5.00E−51 0.52218417 0.799 0.67 1.24E−46 Mcfd2 7.32E−51 0.26358926 0.899 0.643 1.82E−46 1100001G20Rik 1.27E−49 0.29940469 0.993 0.982 3.17E−45 Ndufs8 3.03E−49 0.27492092 0.854 0.607 7.54E−45 Dak 2.23E−48 0.31749445 0.852 0.563 5.54E−44 Ndufb2 2.40E−48 0.29336153 0.888 0.629 5.96E−44 Elovl2 9.90E−48 0.26623714 0.938 0.699 2.46E−43 Orm1 1.29E−47 −0.3040626 0.97 0.952 3.19E−43 Rplp0 5.33E−47 −0.3888413 0.788 0.791 1.32E−42 Pemt 1.55E−46 0.28354116 0.948 0.78 3.86E−42 C8a 4.65E−45 −0.3574056 0.897 0.887 1.15E−40 Akr1c19 9.54E−45 0.26176816 0.821 0.527 2.37E−40 Oaz1 1.95E−44 −0.4482997 0.779 0.75 4.84E−40 Cyp4a12a 6.66E−44 −0.4778521 0.463 0.597 1.65E−39 Serpina3c 1.23E−43 −0.5143596 0.195 0.385 3.05E−39 C8b 1.58E−43 −0.335278 0.953 0.881 3.93E−39 Cideb 1.82E−43 0.26185632 0.892 0.676 4.52E−39 Col18a1 4.74E−41 0.25271374 0.941 0.79 1.18E−36 Gsta3 2.08E−40 −0.2675808 0.993 0.956 5.17E−36 Ugt2b1 2.65E−40 −0.3075642 0.938 0.871 6.59E−36 Rsp14 1.55E−39 −0.3000601 0.943 0.917 3.85E−35 Gchfr 9.84E−39 0.25204319 0.953 0.768 2.44E−34 mt-Atp6 4.42E−37 −0.2634338 0.234 0.452 1.10E−32 Mup13 2.44E−36 −0.6330576 0.468 0.546 6.05E−32 Saa2 1.64E−34 −0.3719511 0.049 0.222 4.07E−30 Eef1b2 4.92E−33 −0.3627624 0.851 0.78 1.22E−28 Actb 7.58E−33 −0.278801 0.938 0.886 1.88E−28 Cfh 3.95E−32 −0.2876493 0.943 0.897 9.80E−28 Sparcl1 7.94E−32 −0.253617 0 0.136 1.97E−27 Slco1a1 1.65E−31 −0.3676845 0.865 0.777 4.10E−27 Uqcrq 1.55E−30 −0.2551066 0.98 0.951 3.85E−26 Cyb5b 2.54E−30 −0.3686974 0.787 0.724 6.31E−26 Keg1 4.30E−30 −0.5313206 0.527 0.545 1.07E−25 Mup2 4.37E−30 −0.6018783 0.254 0.392 1.09E−25 Gstm3 4.79E−29 −0.6276519 0.279 0.414 1.19E−24 Inmt 5.27E−29 −0.3314912 0.936 0.884 1.31E−24 Cml2 6.13E−29 −0.2801974 0.905 0.857 1.52E−24 Ttc39c 1.40E−28 −0.3963737 0.696 0.642 3.49E−24 Scd1 6.31E−28 0.29915098 0.982 0.901 1.57E−23 Mup20 1.62E−27 −0.2683861 0.999 1 4.03E−23 Rps2 1.94E−26 −0.3547845 0.775 0.757 4.81E−22 Egfr 2.57E−25 −0.3563097 0.908 0.809 6.38E−21 Cfhr2 5.00E−25 −0.3089882 0.946 0.868 1.24E−20 Thrsp 6.63E−24 −0.5876996 0.697 0.627 1.65E−19 Hamp 1.08E−23 −0.2994038 0.864 0.884 2.67E−19 Leap2 5.80E−23 0.25433574 0.833 0.632 1.44E−18 Gm4076 8.06E−23 −0.3148234 0.057 0.184 2.00E−18 Cyp2f2 1.22E−22 0.25135427 0.912 0.863 3.03E−18 Ankrd55 8.13E−22 −0.7865348 0.833 0.696 2.02E−17 Hsd17b2 1.06E−21 −0.3251185 0.767 0.711 2.63E−17 Igfbp1 1.21E−17 −0.2514632 0.744 0.717 3.01E−13 Slc22a30 1.29E−16 −0.3628576 0.497 0.493 3.21E−12 Cyp7a1 2.60E−16 −0.2737711 0.143 0.259 6.44E−12 Gm20594 3.73E−16 −0.4169188 0.186 0.294 9.27E−12 Rpl32 4.05E−16 −0.3042904 0.835 0.757 1.01E−11 Ndufb11 5.15E−16 −0.2689829 0.802 0.735 1.28E−11 Hspe1 3.93E−14 −0.323232 0.582 0.557 9.76E−10 Rarres1 8.16E−13 −0.2957998 0.374 0.42 2.03E−08 mmu-mir-6236 1.23E−12 −0.2819002 0.911 0.837 3.06E−08 Slco1b2 1.73E−12 0.27152878 0.996 0.951 4.30E−08 Lect2 1.80E−12 −0.2645229 0.318 0.414 4.48E−08 Tlcd2 3.11E−12 −0.3052345 0.573 0.536 7.73E−08 Bst2 1.23E−11 −0.3075801 0.591 0.54 3.06E−07 Glul 1.75E−11 0.54377904 0.308 0.18 4.36E−07 Cyp2c67 2.22E−11 −0.2853612 0.36 0.418 5.52E−07 Hsd3b3 2.39E−11 −0.2879231 0.664 0.605 5.94E−07 Acss2 6.15E−11 −0.3108047 0.685 0.574 1.53E−06 Mup1 1.46E−10 −0.5088135 0.619 0.583 3.61E−06 Nme1 1.61E−10 −0.2976676 0.742 0.622 4.00E−06 Selk 1.42E−09 −0.3116864 0.532 0.486 3.52E−05 C6 1.16E−08 −0.2909762 0.725 0.642 0.00028737 Rps8 2.26E−08 −0.2891652 0.502 0.471 0.00056072 Cxcl1 8.10E−08 −0.2564732 0.264 0.314 0.00201077 Adh6-ps1 2.80E−07 −0.2741169 0.284 0.313 0.00695696 Pnpla7 6.51E−07 −0.2689142 0.677 0.572 0.01616347 1500017E21Rik 6.87E−07 −0.2767539 0.511 0.476 0.01704927 Rpl36a1 5.46E−06 −0.2835914 0.643 0.551 0.13560354 Ndufb4 1.01E−05 −0.262186 0.554 0.49 0.24969401 Rpl34 0.00330931 −0.2548221 0.445 0.398 1 Acly 0.00429145 −0.2626893 0.537 0.445 1 Ubb 0.0845165 −0.2608023 0.542 0.45 1 Slc1a2 0.09580614 0.26120345 0.055 0.042 1 Ftl1 0.23123934 −0.3160431 0.504 0.409 1 Rpl41 0.66932474 −0.3294678 0.331 0.278 1 Cyp2b10 0.90869564 −0.2984609 0.723 0.542 1

TABLE 4b Differentially expressed genes between time point A48A96 and untreated (UT). ID p_val avg_logFC pct.1 pct.2 p_val_adj Cyp4a14 0 1.704093543 0.984 0.431 0 Cyp4a10 0 1.135370857 0.983 0.657 0 Mat1a 0 1.000433202 1 0.966 0 Apoc2 0 0.782126085 0.943 0.802 0 Chchd10 0 0.720691838 0.994 0.944 0 Angptl3 0 0.7089371 0.996 0.944 0 Hmgcs2 0 0.629289122 0.998 0.986 0 Apoe 0 0.407256897 1 1 0 Serpina1e 0 −0.662045945 0.988 0.999 0 mt-Nd5 0 −0.799147191 0.977 0.995 0 mt-Cytb 0 −0.8545555 0.993 0.999 0 mt-Nd2 0 −0.898054789 0.994 0.999 0 mt-Nd4 0 −0.936405909 0.992 0.998 0 Mup21 0 −1.008171912 0.729 0.929 0 mt-Co1 0 −1.043307563 0.989 0.999 0 Gm13775 0 −1.07808822 0.311 0.761 0 Mup16 0 −1.100681479 0.646 0.934 0 Mup7 0 −1.115587848 0.934 0.998 0 Nudt7 0 −1.14157535 0.674 0.83 0 Selenbp2 0 −1.190221952 0.715 0.937 0 Mup18 0 −1.590870011 0.906 0.997 0 Mup11 0 −1.621134615 0.9 1 0 Mup19 0 −1.730868177 0.955 1 0 Mup9 0 −1.93588422 0.603 0.976 0 Mup6 0 −2.032084932 0.834 0.992 0 Mup17 0 −2.09635042 0.97 1 0 Ttpa  1.7348507452971e−317 0.601240096 0.986 0.869 4.30798137072176e−313 Ces1c 9.12743755309997e−311 0.466837177 0.999 0.985  2.27E−306 mt-Nd1  2.58E−308 −0.591646758 0.998 1  6.39E−304 Retsat  3.87E−303 0.681307283 0.973 0.83  9.61E−299 Cdo1  1.81E−299 0.517045053 0.997 0.96  4.49E−295 mt-Rnr2  3.93E−280 −0.559446336 1 1  9.76E−276 Mup15  2.41E−278 −1.26121256 0.184 0.617  5.98E−274 Apoh  1.27E−276 0.411790107 0.998 0.986  3.16E−272 Saa1  2.92E−263 −1.078220383 0.318 0.662  7.26E−259 Hsd3b5  7.75E−256 −0.830145941 0.277 0.587  1.92E−251 Mup5  1.09E−253 −1.351810718 0.6 0.839  2.70E−249 Mup3  3.11E−251 −0.379596014 1 1  7.72E−247 Apoc1  1.38E−241 0.392095407 1 0.999  3.42E−237 Sepp1  9.85E−239 0.33970689 1 1  2.45E−234 Sult1a1  3.66E−236 0.560453494 0.924 0.707  9.10E−232 Hrg  8.23E−233 0.518895355 0.957 0.831  2.04E−228 Mfsd2a  2.44E−230 0.612232714 0.58 0.148  6.07E−226 Agt  9.72E−229 0.520454244 0.949 0.817  2.41E−224 mt-Rnr1  5.60E−214 −0.485399855 1 1  1.39E−209 Ankrd55  2.17E−211 −0.974280427 0.678 0.696  5.38E−207 Ndrg2  2.43E−211 0.41219937 0.993 0.939  6.03E−207 Mup12  6.39E−210 −0.767698995 0.668 0.86  1.59E−205 Lifr  1.86E−209 −0.563681141 0.618 0.694  4.62E−205 Thrsp  4.77E−209 −0.689057582 0.576 0.627  1.18E−204 Gstp1  6.36E−208 −0.855831436 0.681 0.822  1.58E−203 Snord118  6.27E−207 0.617425052 0.671 0.248  1.56E−202 Ahsg  7.66E−203 0.292489576 1 1  1.90E−198 mt-Co3  7.66E−203 −0.915108473 0.213 0.603  1.90E−198 Ttr  1.30E−198 0.388907438 1 1  3.23E−194 Slco1a4  5.66E−197 0.552641329 0.646 0.238  1.41E−192 Herpud1  2.45E−196 0.513571228 0.945 0.803  6.08E−192 mt-Co2  1.16E−193 −0.918784455 0.221 0.629  2.88E−189 Keg1  4.42E−188 −0.521611435 0.457 0.545  1.10E−183 Igfbp4  1.13E−187 0.43528879 0.978 0.866  2.80E−183 Akr1c6  5.38E−186 −0.468988487 0.96 0.971  1.34E−181 Reep6  2.43E−184 0.514272451 0.931 0.794  6.05E−180 Cp  4.92E−184 0.436243259 0.994 0.943  1.22E−179 Aldob  1.31E−183 0.365460648 0.999 0.996  3.24E−179 Abcd2  1.68E−177 0.285090597 0.366 0.052  4.17E−173 Abcb4  6.95E−177 0.494736917 0.919 0.675  1.73E−172 Gm23935  7.08E−176 0.50194422 0.994 0.925  1.76E−171 Cyp7b1  1.38E−173 −0.542403458 0.67 0.757  3.43E−169 St3gal5  4.05E−172 0.542378437 0.818 0.49  1.01E−167 Slc25a47  5.63E−172 0.502661475 0.977 0.927  1.40E−167 Decr1  2.17E−169 0.466364339 0.889 0.694  5.38E−165 Fth1  3.96E−168 0.378367166 0.994 0.978  9.82E−164 Slc27a2  3.59E−167 0.385256962 0.992 0.949  8.93E−163 Pabpc1  2.52E−164 0.494914201 0.844 0.592  6.27E−160 Ttc36  5.61E−163 0.38128834 0.988 0.95  1.39E−158 Rdh7  4.71E−160 0.364161562 0.995 0.969  1.17E−155 Mup8  1.32E−159 −0.79575704 0.084 0.373  3.27E−155 Lcat  5.85E−158 0.436082968 0.932 0.781  1.45E−153 Gc  7.12E−157 0.259816642 1 0.999  1.77E−152 Ube2r2  3.35E−153 0.46659877 0.819 0.525  8.31E−149 Hmgcl  4.83E−152 0.473794522 0.916 0.729  1.20E−147 Grn  5.47E−152 0.473252349 0.743 0.396  1.36E−147 Mup20  7.34E−152 −0.476207303 0.998 1  1.82E−147 Mup4  2.86E−151 −0.953101828 0.801 0.898  7.09E−147 Apoc3  2.12E−150 0.327008256 1 0.993  5.26E−146 Aldh9a1  5.77E−148 0.415934269 0.926 0.763  1.43E−143 Hspa8  8.18E−148 0.420379148 0.93 0.756  2.03E−143 Egfr  9.84E−147 −0.473388687 0.806 0.809  2.44E−142 F2  2.22E−145 0.32133198 0.998 0.969  5.51E−141 Ttc39c  1.58E−142 −0.374504475 0.625 0.642  3.91E−138 Rbp4  1.96E−142 0.301440617 1 0.999  4.88E−138 Serpina3c  3.94E−141 −0.472511045 0.201 0.385  9.79E−137 Amy1  4.69E−141 0.432738347 0.89 0.676  1.16E−136 Serpina3m  6.01E−140 0.432583404 0.885 0.722  1.49E−135 Elovl3  2.08E−139 −0.442652848 0.736 0.827  5.17E−135 Apoa5  1.53E−138 0.323188383 0.993 0.974  3.80E−134 Serping1  6.04E−137 0.41280952 0.96 0.87  1.50E−132 Rpl38  7.83E−137 0.254329206 0.482 0.16  1.95E−132 Cyp2c70  9.28E−137 −0.395158527 0.859 0.834  2.30E−132 Gyk  2.15E−136 0.402444184 0.702 0.35  5.33E−132 Crat  2.27E−136 0.255626614 0.474 0.15  5.64E−132 C9  6.07E−134 −0.427055258 0.926 0.938  1.51E−129 Wbp1l  2.25E−133 0.440462928 0.853 0.606  5.58E−129 Gstt3  2.25E−133 0.350739865 0.645 0.286  5.59E−129 Decr2  5.16E−133 0.418851877 0.87 0.634  1.28E−128 Tmbim6  9.26E−133 0.338652766 0.992 0.942  2.30E−128 Mup14  2.38E−132 −0.760766854 0.4 0.616  5.90E−128 Ildr2  7.46E−131 0.267607713 0.479 0.159  1.85E−126 Atp5h  1.29E−130 0.434163543 0.893 0.682  3.20E−126 Nr1i3  1.67E−129 0.425883248 0.725 0.377  4.15E−125 Cyp3a25  2.41E−129 0.318573266 0.988 0.919  5.98E−125 Lipa  2.95E−129 0.41833763 0.851 0.61  7.32E−125 Oaz1  3.92E−129 −0.418528822 0.715 0.75  9.74E−125 Oaf  1.31E−128 0.403567608 0.928 0.794  3.26E−124 Scd1  1.93E−128 0.519218079 0.985 0.901  4.78E−124 Atp5k  2.65E−128 0.408878378 0.889 0.678  6.59E−124 Plin5  2.96E−128 0.352087102 0.667 0.315  7.34E−124 Rgs16  3.78E−128 0.322559157 0.415 0.113  9.40E−124 Prdx1  1.61E−127 −0.361890861 0.934 0.927  4.01E−123 Cox5a  3.24E−127 0.40236048 0.88 0.702  8.04E−123 Car3  2.20E−125 −0.405308591 0.97 0.974  5.47E−121 Asl  4.60E−125 0.438458339 0.926 0.787  1.14E−120 Hsd3b7  1.98E−124 −0.382738321 0.777 0.798  4.92E−120 Acat1  3.21E−124 0.368871999 0.949 0.838  7.96E−120 Mup13  5.23E−124 −0.55255936 0.444 0.546  1.30E−119 Rplp0  6.61E−124 −0.430901519 0.707 0.791  1.64E−119 Acbd5  2.77E−123 0.385608793 0.909 0.708  6.87E−119 Agpat6  2.85E−123 0.396260224 0.817 0.517  7.07E−119 Cox8a  9.05E−122 0.44171223 0.818 0.621  2.25E−117 Bfar  3.09E−121 0.290332897 0.61 0.27  7.66E−117 Vtn  6.34E−121 0.333811366 0.998 0.983  1.57E−116 C8b  3.83E−117 −0.360171247 0.894 0.881  9.52E−113 Sdhc  2.51E−116 0.394392518 0.839 0.63  6.24E−112 Slc27a5  3.14E−116 0.336994904 0.973 0.893  7.79E−112 Dhcr24  8.17E−116 0.387274317 0.944 0.783  2.03E−111 Snord13  2.01E−113 0.261078586 0.478 0.175  4.98E−109 Ppara  6.59E−113 0.35885744 0.729 0.407  1.64E−108 Slc25a20  8.33E−113 0.380017899 0.78 0.498  2.07E−108 Slc40a1  3.89E−111 0.356026755 0.653 0.328  9.66E−107 Acss2  2.82E−110 −0.258362678 0.611 0.574  7.00E−106 Brap  4.77E−110 0.349229859 0.741 0.427  1.19E−105 Sult1d1  1.78E−109 0.45987026 0.898 0.684  4.42E−105 Tgoln1  6.82E−109 0.38833408 0.828 0.575  1.69E−104 Slc4a4  9.50E−109 0.331670131 0.661 0.336  2.36E−104 D17Wsu92e  2.20E−108 0.371951808 0.844 0.588  5.47E−104 Gm6484  4.91E−108 0.304268201 0.472 0.174  1.22E−103 Acot12  5.33E−107 0.307840041 0.743 0.425  1.32E−102 Vnn3  8.28E−107 0.276458974 0.555 0.241  2.06E−102 Bnip3  2.17E−106 0.403206563 0.8 0.55  5.38E−102 Sh3glb1  7.00E−106 0.326006747 0.571 0.258  1.74E−101 Tmed5  1.13E−105 0.345007803 0.792 0.492  2.80E−101 Mia3  2.04E−105 0.364623797 0.863 0.61  5.08E−101 Gm2a  2.30E−105 0.383109253 0.714 0.427  5.71E−101 Lpin2  3.75E−105 0.385908326 0.855 0.597  9.32E−101 Slco1a1  2.50E−104 −0.295640242 0.823 0.777  6.20E−100 Sec14l2  2.77E−104 0.321333578 0.961 0.856  6.87E−100 Atp5b  6.90E−104 0.291727476 0.99 0.942 1.71E−99 Zfp91  1.18E−103 0.370686172 0.779 0.492 2.92E−99 Cyp2a12  4.26E−103 0.374332361 0.952 0.884 1.06E−98 0610005C13Rik  5.95E−103 0.34237016 0.884 0.653 1.48E−98 Uroc1  1.08E−102 0.416226092 0.825 0.615 2.68E−98 Nme1  5.87E−102 −0.285705103 0.657 0.622 1.46E−97 Mtdh  1.64E−101 0.30466184 0.739 0.428 4.08E−97 Eef1b2  4.83E−101 −0.317323205 0.8 0.78 1.20E−96 Acad11  1.54E−100 0.357135026 0.809 0.564 3.83E−96 Ass1  2.76E−100 −0.314400604 0.971 0.962 6.84E−96 Camk2n1  4.05E−100 0.250109512 0.586 0.278 1.01E−95 Akr1d1  5.03E−100 0.361037667 0.79 0.515 1.25E−95 Dennd5b 8.13E−99 0.266493539 0.643 0.334 2.02E−94 Ephx2 1.62E−98 0.281258562 0.981 0.937 4.03E−94 Scp2 1.84E−98 −0.325161752 0.988 0.986 4.57E−94 Serpinf1 3.42E−98 0.319550979 0.956 0.864 8.50E−94 Acadl 6.56E−98 0.316216015 0.862 0.612 1.63E−93 Slc22a30 7.73E−98 −0.295400819 0.461 0.493 1.92E−93 Cpt1a 3.10E−97 0.372935212 0.868 0.651 7.70E−93 Cyp2c44 7.78E−97 0.385935584 0.879 0.698 1.93E−92 Mgll 9.00E−97 0.333899751 0.743 0.449 2.24E−92 Ces1b 9.68E−97 0.372958858 0.717 0.437 2.40E−92 Chpt1 1.79E−96 0.35662056 0.882 0.664 4.45E−92 Bche 2.34E−96 0.313419985 0.675 0.369 5.82E−92 Hes6 7.85E−96 −0.262263942 0.415 0.42 1.95E−91 BC025446 8.95E−96 0.272610935 0.611 0.306 2.22E−91 Gstm3 1.32E−95 −0.598573335 0.256 0.414 3.28E−91 Slc25a10 2.78E−95 0.343272504 0.794 0.536 6.91E−91 Abcc3 4.53E−95 0.363799323 0.8 0.542 1.13E−90 Rsp14 7.49E−95 −0.348405505 0.908 0.917 1.86E−90 Gfra1 1.15E−94 0.320843264 0.782 0.498 2.86E−90 Rdx 1.46E−94 0.318521875 0.874 0.63 3.62E−90 Pex11a 1.66E−94 0.350827626 0.738 0.441 4.11E−90 Tmbim4 2.87E−94 0.32269634 0.689 0.394 7.12E−90 Selk 1.39E−93 −0.289300641 0.467 0.486 3.45E−89 Rpl4 3.80E−93 0.283935593 0.977 0.915 9.43E−89 Aplp2 4.37E−93 0.33938781 0.86 0.625 1.08E−88 Mup2 1.14E−92 −0.55305847 0.255 0.392 2.83E−88 Apoa4 8.99E−92 0.495579268 0.62 0.339 2.23E−87 Pnpla7 9.47E−92 −0.301626901 0.572 0.572 2.35E−87 Kif1b 2.14E−91 0.299610278 0.732 0.435 5.33E−87 Serp1 2.20E−91 −0.267566027 0.76 0.721 5.46E−87 CtagcS 1.97E−90 0.328678207 0.892 0.683 4.89E−86 Fah 6.12E−90 0.302494707 0.939 0.834 1.52E−85 Hsd17b13 1.23E−89 0.550399594 0.85 0.74 3.06E−85 Tmem56 4.57E−89 0.335238196 0.847 0.612 1.14E−84 Comt 6.00E−89 −0.286248465 0.932 0.931 1.49E−84 Slc10a1 7.28E−89 0.314325805 0.961 0.843 1.81E−84 Sparcl1 9.28E−89 −0.253616986 0 0.136 2.30E−84 Pbld1 3.56E−88 0.322688203 0.807 0.565 8.83E−84 Hsd17b2 5.55E−88 −0.313480586 0.695 0.711 1.38E−83 Abca6 6.11E−88 0.33284944 0.773 0.507 1.52E−83 Saa2 4.41E−87 −0.390082382 0.036 0.222 1.10E−82 Mettl7b 2.12E−86 0.283916114 0.963 0.869 5.26E−82 Atxn7l3b 2.41E−86 0.306239775 0.756 0.476 5.98E−82 Gpld1 3.69E−86 0.328106789 0.816 0.577 9.16E−82 Cfhr2 4.83E−86 −0.306325678 0.917 0.868 1.20E−81 Hsd3b3 1.64E−85 −0.299662144 0.586 0.605 4.08E−81 G0s2 2.06E−85 0.346452213 0.614 0.33 5.12E−81 Prodh2 3.05E−85 0.345294809 0.812 0.611 7.57E−81 Por 6.21E−85 0.33194923 0.891 0.675 1.54E−80 Prdx4 1.37E−84 −0.251975081 0.642 0.607 3.41E−80 Hsd17b10 2.19E−84 0.361579378 0.887 0.7 5.43E−80 Mttp 2.30E−84 0.311504107 0.878 0.697 5.72E−80 Serpina3n 2.31E−84 0.346482791 0.788 0.574 5.73E−80 Hspa5 2.40E−84 0.291184144 0.984 0.944 5.96E−80 Creg1 5.44E−84 0.276773054 0.99 0.926 1.35E−79 Cyp3a11 1.17E−83 0.313927334 0.999 1 2.91E−79 Pnpla8 2.68E−83 0.295631611 0.803 0.544 6.66E−79 Ctsa 2.92E−83 0.252009224 0.615 0.33 7.25E−79 Insig2 5.58E−83 0.300825179 0.95 0.81 1.39E−78 C8a 6.02E−83 −0.327131388 0.882 0.887 1.49E−78 Echs1 7.04E−83 0.318692311 0.935 0.817 1.75E−78 Pigr 1.00E−82 0.386842112 0.967 0.947 2.48E−78 Eif5 2.11E−82 0.284340466 0.918 0.74 5.24E−78 Hnf4a 3.28E−82 0.314710574 0.901 0.743 8.15E−78 Etnppl 3.81E−82 0.496712405 0.777 0.606 9.45E−78 Arhgap5 4.87E−82 0.288514066 0.731 0.454 1.21E−77 Eci2 5.30E−82 0.311004843 0.877 0.698 1.31E−77 Nfe2l1 1.57E−81 0.27034473 0.582 0.303 3.89E−77 Pcbp2 2.09E−81 0.310347013 0.704 0.438 5.18E−77 Actb 2.95E−81 −0.294140078 0.892 0.886 7.34E−77 Cyp1a2 4.20E−81 −0.445766232 0.638 0.794 1.04E−76 Actn4 5.06E−81 0.299765947 0.7 0.425 1.26E−76 Igf1 9.43E−81 0.295791825 0.973 0.904 2.34E−76 Cox6a1 2.01E−80 0.292128773 0.966 0.887 5.00E−76 Tcea3 2.70E−80 0.3163181 0.709 0.439 6.70E−76 Gltscr2 4.30E−80 0.255310647 0.702 0.424 1.07E−75 Gcdh 5.44E−80 0.273385895 0.95 0.85 1.35E−75 Orm1 1.32E−79 −0.31003929 0.947 0.952 3.28E−75 Atf5 1.56E−79 0.329004772 0.832 0.641 3.87E−75 Creb3l3 2.61E−79 0.275700825 0.939 0.831 6.48E−75 Ctsh 5.03E−79 0.32445036 0.883 0.727 1.25E−74 Cxcl12 1.28E−78 0.257250112 0.696 0.419 3.17E−74 Cbr1 2.47E−78 0.260731659 0.672 0.395 6.15E−74 Mlycd 2.57E−78 0.313046697 0.754 0.503 6.38E−74 Aco2 2.89E−78 0.285855791 0.752 0.493 7.18E−74 Maob 6.31E−78 0.32037326 0.804 0.575 1.57E−73 Slc25a13 1.28E−77 0.285473174 0.859 0.655 3.18E−73 Man2a1 1.37E−77 0.332755834 0.8 0.583 3.41E−73 Slco1b2 1.49E−77 0.386023002 0.997 0.951 3.69E−73 Rps2 1.93E−77 −0.374246561 0.697 0.757 4.80E−73 Tomm70a 3.24E−77 0.265762726 0.76 0.494 8.04E−73 Ggnbp2 7.84E−77 0.272604502 0.703 0.43 1.95E−72 Asgr2 1.23E−76 0.306445529 0.785 0.555 3.06E−72 Gabarap 1.23E−76 0.289400057 0.909 0.769 3.06E−72 F10 1.47E−76 0.279095541 0.96 0.895 3.65E−72 Cyp2d26 1.49E−76 0.259136874 0.969 0.903 3.71E−72 Mt1 3.77E−76 0.356326784 0.81 0.556 9.36E−72 Serinc3 4.38E−76 0.292320724 0.697 0.433 1.09E−71 C130074G19Rik 4.54E−76 0.250322698 0.71 0.439 1.13E−71 Suds3 8.94E−75 0.25388963 0.635 0.364 2.22E−70 Ddb1 1.79E−74 0.277809186 0.694 0.428 4.44E−70 Ces1d 3.46E−74 0.285254637 0.98 0.923 8.60E−70 Rps8 1.82E−73 −0.274601282 0.444 0.471 4.51E−69 P4hb 3.56E−73 0.250660872 0.984 0.941 8.83E−69 Tob1 7.22E−73 0.284985634 0.693 0.43 1.79E−68 Hadh 7.72E−73 0.288772268 0.845 0.642 1.92E−68 C3 8.36E−73 0.259166718 0.999 0.99 2.08E−68 Slc7a2 1.29E−72 0.34497807 0.884 0.735 3.21E−68 Gys2 2.56E−72 0.274401611 0.623 0.358 6.36E−68 Klf9 2.74E−72 0.293415875 0.756 0.52 6.80E−68 Ei24 2.82E−72 0.257327011 0.738 0.48 7.01E−68 Sec62 4.20E−72 0.251575572 0.82 0.582 1.04E−67 Dmgdh 5.63E−72 0.265846058 0.923 0.764 1.40E−67 Ppib 7.64E−72 −0.260118322 0.793 0.767 1.90E−67 Abhd14b 2.59E−71 0.299363281 0.78 0.565 6.42E−67 Sord 7.97E−71 0.26850985 0.978 0.931 1.98E−66 Furin 1.72E−70 0.278163716 0.674 0.417 4.27E−66 Shmt1 6.32E−70 0.278820727 0.788 0.556 1.57E−65 Ugp2 8.02E−70 0.297335445 0.904 0.749 1.99E−65 Lamp1 9.89E−70 0.268283663 0.959 0.885 2.46E−65 Khk 1.54E−69 0.310103866 0.963 0.863 3.82E−65 Cd1d1 2.00E−69 0.291156805 0.821 0.612 4.96E−65 Fmo5 3.51E−69 0.252070931 0.959 0.837 8.71E−65 C4b 5.80E−69 0.283273876 0.953 0.883 1.44E−64 Mup1 1.20E−68 −0.556836871 0.525 0.583 2.97E−64 Hspe1 1.32E−68 −0.281318916 0.533 0.557 3.28E−64 Rdh16 1.89E−68 0.269182372 0.525 0.272 4.69E−64 Ndufb11 9.28E−68 −0.275645983 0.739 0.735 2.30E−63 Atp2a2 1.64E−67 0.305636215 0.728 0.495 4.07E−63 Ces3b 1.96E−67 −0.263292817 0.792 0.787 4.87E−63 Acsl1 2.51E−67 0.256335416 0.977 0.924 6.24E−63 Ftl1 3.38E−67 −0.29880847 0.438 0.409 8.39E−63 Lpgat1 1.67E−66 0.257600415 0.747 0.502 4.15E−62 Hsd17b4 4.01E−66 0.253232967 0.943 0.818 9.96E−62 Ifitm3 8.45E−66 −0.254348675 0.823 0.812 2.10E−61 Tmem106b 1.27E−65 0.270357032 0.787 0.557 3.16E−61 Gclm 1.64E−65 0.258765469 0.893 0.712 4.08E−61 F9 4.58E−65 0.256805166 0.836 0.632 1.14E−60 Pipox 5.65E−65 0.272543042 0.774 0.549 1.40E−60 Atp1a1 6.53E−65 0.262770413 0.701 0.457 1.62E−60 Sardh 9.29E−65 0.269183147 0.939 0.838 2.31E−60 Gsta2 1.03E−64 0.252161786 0.583 0.333 2.57E−60 Sdhd 2.03E−64 0.320841923 0.837 0.677 5.04E−60 Gabarapl1 4.17E−64 0.260716513 0.917 0.779 1.04E−59 Inmt 5.29E−64 −0.25322177 0.935 0.884 1.31E−59 Usmg5 2.56E−63 0.278730923 0.677 0.43 6.37E−59 Hgfac 3.33E−63 0.252189991 0.682 0.438 8.26E−59 F12 5.05E−63 0.256737037 0.922 0.814 1.25E−58 Ubxn4 6.14E−63 0.250313647 0.802 0.579 1.52E−58 Rpl41 8.17E−63 −0.294952328 0.304 0.278 2.03E−58 Slc2a2 2.10E−62 0.272297971 0.716 0.479 5.21E−58 Fcgrt 2.17E−62 0.258478842 0.806 0.599 5.39E−58 Rpl32 2.50E−62 −0.284689184 0.766 0.757 6.20E−58 Ubb 3.95E−62 −0.264432797 0.465 0.45 9.81E−58 Fn1 4.84E−62 0.292522175 0.932 0.821 1.20E−57 F5 5.57E−61 0.300566587 0.881 0.728 1.38E−56 Ptms 1.52E−60 0.267838974 0.857 0.689 3.78E−56 Pck1 1.63E−60 0.271859881 0.998 0.987 4.04E−56 Rarres1 1.78E−60 −0.291851226 0.327 0.42 4.42E−56 Hadha 1.24E−59 0.250937029 0.895 0.744 3.08E−55 Atp5d 2.30E−59 0.250062798 0.866 0.712 5.70E−55 Gm4076 9.59E−59 −0.308321155 0.047 0.184 2.38E−54 Ctsd 1.22E−58 0.257862212 0.831 0.656 3.04E−54 Sfxn1 3.83E−58 0.304885886 0.702 0.496 9.52E−54 Ces1e 3.91E−58 0.265618893 0.791 0.576 9.71E−54 C6 1.21E−57 −0.26698766 0.653 0.642 3.00E−53 Upb1 1.58E−57 0.25038758 0.895 0.759 3.92E−53 Ppp2r5a 1.67E−57 0.250897706 0.803 0.594 4.14E−53 Ech1 2.49E−57 0.250481301 0.951 0.856 6.18E−53 Sec61a1 4.01E−57 0.263729835 0.7 0.476 9.95E−53 Slc37a4 2.56E−56 0.268318739 0.717 0.502 6.35E−52 Cyp8b1 2.75E−56 0.282315072 0.905 0.745 6.82E−52 Park7 6.56E−54 0.251517689 0.902 0.784 1.63E−49 Ndufb2 2.41E−50 0.251595204 0.814 0.629 5.98E−46 Serpina12 2.13E−49 −0.324744036 0.38 0.492 5.28E−45 Cyp4a12a 3.63E−48 −0.277051162 0.509 0.597 9.00E−44 Lpin1 2.48E−45 0.277494868 0.515 0.31 6.16E−41 Gm20594 3.69E−41 −0.356558629 0.222 0.294 9.16E−37 Cyp2c54 3.26E−38 0.250387024 0.879 0.759 8.10E−34 mmu-mir-6236 2.88E−35 −0.429737333 0.859 0.837 7.15E−31 Sds 1.58E−34 0.297273523 0.671 0.67 3.93E−30 mt-Atp6 1.02E−32 −0.323426357 0.326 0.452 2.52E−28 Hal 1.03E−25 0.280113531 0.824 0.749 2.55E−21 Aldh3a2 7.57E−18 0.307877353 0.592 0.529 1.88E−13 Glul 6.83E−11 0.379494728 0.257 0.18 1.70E−06

TABLE 4c Differentially expressed genes between time point A96 and untreated (UT) I.D. p_val avg_logFC pct.1 pct.2 p_val_adj Cyp4a14 0 1.600758457 0.975 0.431 0 Mat1a 0 0.932795094 1 0.966 0 Serpina1e 0 −1.134217923 0.977 0.999 0 Mup11 0 −1.558844676 0.905 1 0 Mup9 0 −1.81783443 0.619 0.976 0 Mup17 0 −1.889311872 0.98 1 0 Mup6 0 −2.021370562 0.778 0.992 0 Cyp4a10  2.14E−272 1.120330137 0.974 0.657  5.30E−268 Angptl3  1.84E−268 0.693633109 0.998 0.944  4.57E−264 Selenbp2  3.56E−267 −1.257537093 0.612 0.937  8.83E−263 Apoc1  1.21E−236 0.500838397 1 0.999  3.00E−232 Mup7  6.32E−222 −1.145234189 0.938 0.998  1.57E−217 Mup18  6.63E−216 −1.29677101 0.928 0.997  1.65E−211 Mup16  1.30E−213 −1.118868702 0.567 0.934  3.24E−209 Cdo1  2.68E−208 0.567928382 0.998 0.96  6.65E−204 Chchd10  2.87E−191 0.607996934 0.994 0.944  7.12E−187 Serpina3k  3.14E−181 −0.303639552 1 1  7.78E−177 Apoe  3.87E−176 0.327046521 1 1  9.61E−172 mt-Nd4  4.55E−175 −0.848768513 0.986 0.998  1.13E−170 Ttpa  2.91E−171 0.626576167 0.98 0.869  7.23E−167 Mup20  4.60E−169 −0.777084754 0.996 1  1.14E−164 Mup21  9.94E−166 −0.940012218 0.676 0.929  2.47E−161 Mup19  8.02E−165 −1.257832573 0.973 1  1.99E−160 Scd1  3.56E−164 0.719867652 0.989 0.901  8.84E−160 Mup3  4.46E−164 −0.409813908 1 1  1.11E−159 Ttr  2.21E−163 0.345887189 1 1  5.48E−159 mt-Co1  9.06E−161 −0.845943199 0.983 0.999  2.25E−156 mt-Nd2  7.76E−159 −0.71965104 0.994 0.999  1.93E−154 Gm13775  2.84E−157 −1.050178147 0.3 0.761  7.06E−153 Hmgcs2  9.48E−157 0.423416551 0.996 0.986  2.35E−152 Nudt7  3.13E−150 −1.139673094 0.602 0.83  7.78E−146 mt-Cytb  2.05E−145 −0.710470319 0.99 0.999  5.10E−141 Apoh  3.17E−136 0.346721981 0.998 0.986  7.86E−132 Gstp1  4.53E−134 −1.05972633 0.529 0.822  1.12E−129 mt-Nd1  9.87E−133 −0.584321112 0.996 1  2.45E−128 Mup15  1.46E−130 −1.238690862 0.156 0.617  3.63E−126 Saa1  2.60E−130 −1.157027866 0.232 0.662  6.45E−126 Serpina1b  2.05E−129 −0.384477147 0.996 0.996  5.10E−125 Ces1c  2.77E−127 0.358303072 1 0.985  6.87E−123 Mup12  3.42E−124 −0.833089417 0.571 0.86  8.50E−120 Mup5  2.13E−120 −1.26562348 0.538 0.839  5.30E−116 Sepp1  3.10E−118 0.28385063 1 1  7.69E−114 mt-Co3  6.00E−105 −1.046313505 0.213 0.603  1.49E−100 Zfp683  2.36E−104 0.302737948 0.476 0.116  5.87E−100 Slc27a2  2.28E−102 0.393073566 0.988 0.949 5.65E−98 Ndrg2  1.79E−100 0.380210534 0.985 0.939 4.45E−96 Retsat 4.63E−99 0.533337889 0.957 0.83 1.15E−94 Sult1a1 2.51E−94 0.521965916 0.881 0.707 6.23E−90 Mt1 5.36E−94 0.637988242 0.839 0.556 1.33E−89 Igfbp4 8.30E−94 0.418865013 0.964 0.866 2.06E−89 mt-Nd5 2.10E−93 −0.573016379 0.964 0.995 5.21E−89 Fth1 7.38E−93 0.322617334 0.993 0.978 1.83E−88 Apoc3 7.54E−93 0.300246662 1 0.993 1.87E−88 C9 1.49E−92 −0.513884034 0.89 0.938 3.69E−88 Serpina1c 3.40E−91 −0.317587699 0.998 0.998 8.44E−87 Ces1d 4.28E−91 0.427718067 0.977 0.923 1.06E−86 Hsd3b5 2.20E−88 −0.798118541 0.25 0.587 5.45E−84 Snord118 1.26E−87 0.578283559 0.564 0.248 3.12E−83 Abcb4 3.27E−82 0.47584587 0.878 0.675 8.12E−78 mt-Co2 1.30E−79 −1.033164507 0.313 0.629 3.24E−75 Ankrd55 9.32E−79 −1.238650283 0.503 0.696 2.31E−74 mt-Tp 2.27E−78 0.308472055 0.329 0.083 5.63E−74 Hrg 2.56E−78 0.40951941 0.923 0.831 6.37E−74 Slco1b2 7.71E−78 0.50085864 0.998 0.951 1.91E−73 Hspa8 1.28E−76 0.425734559 0.905 0.756 3.19E−72 Egfr 1.83E−75 −0.623880361 0.691 0.809 4.55E−71 Apoc2 6.30E−75 0.518676481 0.901 0.802 1.57E−70 Mettl7b 2.67E−74 0.378385546 0.949 0.869 6.64E−70 Pltp 4.26E−74 0.291854911 0.237 0.045 1.06E−69 Crot 1.15E−73 0.332587455 0.989 0.942 2.86E−69 Acbd5 2.82E−73 0.434071255 0.87 0.708 6.99E−69 Chpt1 1.82E−68 0.442418636 0.848 0.664 4.53E−64 Mfsd2a 2.72E−68 0.380198802 0.41 0.148 6.75E−64 Gyk 4.10E−68 0.43344086 0.616 0.35 1.02E−63 Atp5k 5.72E−68 0.40683529 0.837 0.678 1.42E−63 Slco1a4 2.83E−67 0.465182557 0.507 0.238 7.02E−63 Cyp3a11 4.60E−67 0.262520214 0.999 1 1.14E−62 Agt 9.05E−67 0.376513419 0.912 0.817 2.25E−62 Mup8 1.05E−66 −0.78705351 0.067 0.373 2.61E−62 Lipa 1.52E−66 0.437590517 0.791 0.61 3.78E−62 Asl 1.71E−66 0.414122541 0.896 0.787 4.26E−62 Aldh2 1.95E−66 0.304046608 0.995 0.973 4.84E−62 Mup14 4.19E−66 −0.794252292 0.335 0.616 1.04E−61 Amy1 3.46E−64 0.421164278 0.831 0.676 8.59E−60 Rdh7 4.17E−64 0.267142418 0.995 0.969 1.04E−59 Ube2r2 5.94E−64 0.424389458 0.747 0.525 1.48E−59 mt-Rnr1 2.84E−63 −0.339795422 1 1 7.04E−59 Ubc 3.45E−63 0.357786823 0.968 0.872 8.58E−59 Thrsp 5.64E−62 −0.816880004 0.44 0.627 1.40E−57 C3 5.68E−62 0.261580397 0.998 0.99 1.41E−57 mt-Rnr2 1.26E−61 −0.333163796 1 1 3.12E−57 Slc4a4 3.45E−61 0.402545626 0.609 0.336 8.57E−57 Pex11a 7.21E−61 0.462020512 0.7 0.441 1.79E−56 Phyh 9.71E−61 0.254119045 0.998 0.986 2.41E−56 Tmem56 3.46E−60 0.402560106 0.812 0.612 8.58E−56 Rplp0 1.41E−59 −0.480428304 0.617 0.791 3.50E−55 Agpat6 1.75E−59 0.409826612 0.743 0.517 4.34E−55 Cyp7b1 1.13E−58 −0.535025845 0.585 0.757 2.81E−54 Acot4 2.69E−58 0.268017172 0.328 0.105 6.69E−54 Aplp2 6.80E−58 0.385893889 0.826 0.625 1.69E−53 Insig2 9.53E−58 0.35940331 0.928 0.81 2.37E−53 Aldh9a1 1.53E−57 0.363277407 0.884 0.763 3.81E−53 Rsp14 2.79E−57 −0.405734932 0.869 0.917 6.92E−53 Tmed5 3.82E−57 0.375398251 0.714 0.492 9.48E−53 Dhcr24 7.47E−57 0.384204715 0.933 0.783 1.85E−52 Akr1c6 9.53E−57 −0.359039536 0.967 0.971 2.37E−52 Cpt1a 1.90E−56 0.374218574 0.837 0.651 4.73E−52 Cp 2.07E−56 0.282591145 0.993 0.943 5.14E−52 Cyp8b1 8.62E−56 0.416953547 0.897 0.745 2.14E−51 Decr2 1.16E−55 0.372833523 0.813 0.634 2.89E−51 Sult1d1 2.45E−55 0.442093823 0.855 0.684 6.09E−51 Tmbim6 2.64E−55 0.262388341 0.988 0.942 6.56E−51 Acat1 7.06E−55 0.348475979 0.917 0.838 1.75E−50 Rdx 5.04E−54 0.367980343 0.824 0.63 1.25E−49 Crat 5.43E−54 0.262436474 0.389 0.15 1.35E−49 Cyp3a25 3.67E−53 0.281153449 0.981 0.919 9.11E−49 Prlr 6.12E−53 0.361079861 0.574 0.316 1.52E−48 Kif1b 6.31E−53 0.390898595 0.686 0.435 1.57E−48 Tgoln1 2.31E−52 0.380103515 0.756 0.575 5.74E−48 Akr1d1 1.08E−51 0.378695209 0.721 0.515 2.68E−47 Grn 1.32E−51 0.373090696 0.629 0.396 3.27E−47 Acsl1 3.10E−51 0.291538271 0.977 0.924 7.69E−47 Lcat 4.49E−51 0.329386736 0.886 0.781 1.12E−46 C8b 5.02E−51 −0.388933382 0.827 0.881 1.25E−46 Pabpc1 1.07E−50 0.369312616 0.766 0.592 2.66E−46 Hmgcl 1.10E−50 0.352973298 0.871 0.729 2.72E−46 Serpina12 9.77E−50 −0.532616287 0.226 0.492 2.43E−45 Mia3 1.63E−49 0.35629328 0.81 0.61 4.06E−45 Ces3a 2.69E−49 −0.284381139 0.97 0.967 6.69E−45 Tob1 3.05E−49 0.373100971 0.649 0.43 7.58E−45 Gstt3 3.52E−49 0.337898035 0.541 0.286 8.74E−45 Trp53inp1 4.76E−49 0.364652102 0.551 0.308 1.18E−44 St3gal5 7.54E−48 0.38618033 0.71 0.49 1.87E−43 Nr1i3 8.17E−48 0.373496949 0.625 0.377 2.03E−43 Serpina1a 3.10E−47 −0.270847162 0.991 0.991 7.70E−43 Hpx 3.37E−47 −0.264031877 0.998 0.997 8.37E−43 D17Wsu92e 4.32E−47 0.358105893 0.771 0.588 1.07E−42 Wbp1l 1.07E−46 0.345645814 0.789 0.606 2.66E−42 Gclm 2.21E−46 0.328178558 0.865 0.712 5.50E−42 Nfe2l2 5.21E−46 0.304823522 0.465 0.229 1.29E−41 Lifr 6.77E−46 −0.487526847 0.556 0.694 1.68E−41 Atp5h 1.28E−45 0.311372918 0.848 0.682 3.18E−41 Cox5a 2.96E−45 0.339787139 0.813 0.702 7.36E−41 Cxcl12 7.95E−45 0.337162418 0.635 0.419 1.97E−40 F5 1.42E−44 0.355721719 0.858 0.728 3.52E−40 Zfp91 1.78E−44 0.374122215 0.693 0.492 4.42E−40 Mtdh 5.57E−44 0.32095866 0.649 0.428 1.38E−39 Hhex 8.35E−44 0.320918894 0.543 0.307 2.07E−39 Acadl 1.56E−43 0.293654435 0.8 0.612 3.88E−39 Ppp2r5a 2.98E−43 0.34926081 0.764 0.594 7.41E−39 Creg1 5.93E−43 0.258648182 0.985 0.926 1.47E−38 Slc40a1 6.14E−43 0.336008423 0.551 0.328 1.52E−38 Cpeb4 6.82E−43 0.341793976 0.527 0.299 1.69E−38 Sec14l2 8.99E−43 0.272359641 0.939 0.856 2.23E−38 Rdh16 1.13E−42 0.371605381 0.494 0.272 2.80E−38 Ctage5 1.16E−42 0.321725387 0.837 0.683 2.88E−38 Orm1 1.31E−42 −0.316805138 0.921 0.952 3.25E−38 Brap 1.56E−42 0.311271816 0.642 0.427 3.86E−38 Ptms 7.41E−42 0.324316442 0.806 0.689 1.84E−37 Acot12 1.09E−41 0.295700709 0.65 0.425 2.71E−37 Bche 1.31E−41 0.328717474 0.588 0.369 3.26E−37 Reep6 1.56E−41 0.319298739 0.891 0.794 3.87E−37 Sdhc 2.99E−41 0.318089739 0.76 0.63 7.41E−37 Tsc22d3 4.68E−41 0.342532759 0.534 0.312 1.16E−36 Slc25a20 5.32E−41 0.321484297 0.671 0.498 1.32E−36 Gabarapl1 1.41E−40 0.298356288 0.881 0.779 3.51E−36 Abcc3 1.58E−40 0.330441312 0.733 0.542 3.92E−36 Herpud1 1.87E−40 0.333265347 0.9 0.803 4.64E−36 Saa2 1.89E−40 −0.410878051 0.021 0.222 4.69E−36 Decr1 2.56E−40 0.32410256 0.808 0.694 6.37E−36 Cyp2c29 3.17E−40 0.410041422 0.962 0.93 7.87E−36 Acot1 3.54E−40 0.298047999 0.459 0.237 8.79E−36 Snord13 3.63E−40 0.265918809 0.386 0.175 9.03E−36 Eif5 3.95E−40 0.274902626 0.879 0.74 9.80E−36 Por 5.68E−40 0.333398957 0.858 0.675 1.41E−35 Tmem106b 9.20E−40 0.328514628 0.727 0.557 2.28E−35 Keg1 1.10E−39 −0.510801616 0.378 0.545 2.73E−35 Dusp6 2.04E−39 0.324885631 0.476 0.261 5.06E−35 Arl4a 2.96E−39 0.291095527 0.517 0.294 7.36E−35 Slc27a5 3.04E−39 0.256735017 0.958 0.893 7.54E−35 Elovl5 3.57E−39 0.323186895 0.765 0.58 8.86E−35 Cd36 4.53E−39 0.331236859 0.299 0.123 1.12E−34 Pnp1a8 8.92E−39 0.308301577 0.723 0.544 2.21E−34 0610005C13Rik 1.18E−38 0.29785727 0.816 0.653 2.92E−34 Aqp9 2.73E−38 0.334613695 0.801 0.647 6.79E−34 Bnip3 4.39E−38 0.344268713 0.716 0.55 1.09E−33 Ppara 4.46E−38 0.305514783 0.614 0.407 1.11E−33 Cyp2c44 6.48E−38 0.325839576 0.828 0.698 1.61E−33 Zfp36l1 6.59E−38 0.329804827 0.601 0.402 1.64E−33 Comt 1.09E−37 −0.269092283 0.902 0.931 2.70E−33 Aldh3a2 1.63E−37 0.493314482 0.687 0.529 4.05E−33 Ildr2 3.24E−37 0.25094453 0.356 0.159 8.06E−33 Man2a1 3.28E−37 0.332441099 0.737 0.583 8.15E−33 Gpld1 4.00E−37 0.303852677 0.748 0.577 9.92E−33 Hamp 4.80E−37 0.339616236 0.92 0.884 1.19E−32 Ddx3x 4.94E−37 0.289927181 0.701 0.513 1.23E−32 Uhrf1bp1l 5.68E−37 0.255854149 0.415 0.207 1.41E−32 Palmd 6.66E−37 0.25838388 0.43 0.219 1.65E−32 Serpinf1 9.62E−37 0.257223443 0.934 0.864 2.39E−32 Cox6a1 1.26E−36 0.251744129 0.943 0.887 3.14E−32 Pcbp2 1.53E−36 0.311286813 0.621 0.438 3.81E−32 Tat 2.43E−36 0.25292193 0.981 0.903 6.04E−32 Actb 2.77E−36 −0.311680152 0.839 0.886 6.88E−32 Hnf4a 4.21E−36 0.282370809 0.858 0.743 1.05E−31 Mttp 8.85E−36 0.275504341 0.816 0.697 2.20E−31 Prkd3 9.88E−36 0.30495006 0.682 0.49 2.45E−31 Dpys 1.26E−35 0.262645107 0.824 0.682 3.12E−31 Plin5 1.41E−35 0.266317901 0.532 0.315 3.51E−31 Hsd17b7 2.01E−35 0.305636008 0.56 0.353 4.99E−31 Dhdh 3.32E−35 0.283722648 0.734 0.583 8.24E−31 Pten 3.91E−35 0.302502242 0.64 0.458 9.71E−31 Hsd17b10 7.23E−35 0.309165601 0.841 0.7 1.80E−30 Pbld1 9.61E−35 0.281095523 0.723 0.565 2.39E−30 Hpgd 1.02E−34 0.339771108 0.588 0.394 2.53E−30 Secisbp2l 1.16E−34 0.278110109 0.529 0.317 2.87E−30 Lpin2 1.38E−34 0.284091908 0.781 0.597 3.44E−30 Dmgdh 2.94E−34 0.263486277 0.89 0.764 7.31E−30 Cox8a 3.32E−34 0.308861116 0.737 0.621 8.24E−30 Slc25a13 4.31E−34 0.257252303 0.786 0.655 1.07E−29 Dennd5b 5.86E−34 0.28707652 0.548 0.334 1.46E−29 Ei24 6.16E−34 0.271840234 0.667 0.48 1.53E−29 Nfe2l1 7.85E−34 0.290178531 0.508 0.303 1.95E−29 Brd2 7.88E−34 0.310435276 0.601 0.408 1.96E−29 Gsta2 8.87E−34 0.311098868 0.522 0.333 2.20E−29 Oaz1 1.04E−33 −0.38606735 0.643 0.75 2.57E−29 Ugp2 1.31E−33 0.293401416 0.858 0.749 3.26E−29 Rps2 1.54E−33 −0.396600754 0.609 0.757 3.83E−29 Cpox 1.57E−33 0.332618644 0.634 0.45 3.89E−29 D4Wsu53e 1.67E−33 0.303195253 0.597 0.385 4.14E−29 Ncl 4.23E−33 0.280946095 0.731 0.567 1.05E−28 Etfdh 4.77E−33 0.280245636 0.811 0.7 1.18E−28 Slc7a2 6.50E−33 0.295894626 0.843 0.735 1.61E−28 Igfbp1 6.60E−33 0.311528043 0.826 0.717 1.64E−28 Eif4g2 1.44E−32 0.283785981 0.812 0.678 3.58E−28 Fn1 1.75E−32 0.271755563 0.917 0.821 4.34E−28 Cbr1 1.75E−32 0.282855589 0.591 0.395 4.35E−28 Cyp2c54 2.81E−32 0.304653347 0.86 0.759 6.98E−28 Chp1 8.03E−32 0.268716501 0.687 0.515 1.99E−27 G0s2 1.20E−31 0.294687604 0.525 0.33 2.98E−27 Hamp2 1.29E−31 0.305192386 0.203 0.07 3.19E−27 Slc25a47 1.92E−31 0.277696086 0.96 0.927 4.76E−27 Abca6 2.14E−31 0.282291899 0.686 0.507 5.31E−27 Gfra1 2.84E−31 0.257142102 0.687 0.498 7.06E−27 Ces3b 3.07E−31 −0.3398386 0.685 0.787 7.61E−27 Gclc 3.30E−31 0.270711809 0.839 0.718 8.19E−27 Lpgat1 5.34E−31 0.274988157 0.671 0.502 1.33E−26 Serpina3c 1.26E−30 −0.427440346 0.209 0.385 3.12E−26 Hadh 1.40E−30 0.26259162 0.774 0.642 3.47E−26 Gm2a 1.47E−30 0.316388243 0.587 0.427 3.66E−26 Tomm70a 1.62E−30 0.267009116 0.67 0.494 4.03E−26 Acad11 1.64E−30 0.257789155 0.711 0.564 4.08E−26 Csde1 1.66E−30 0.256715528 0.742 0.577 4.12E−26 Atxn7l3b 2.35E−30 0.282811183 0.654 0.476 5.85E−26 Pxmp4 3.17E−30 0.27943845 0.687 0.526 7.88E−26 Slc25a10 4.53E−30 0.250772586 0.701 0.536 1.12E−25 Nucks1 5.40E−30 0.250923367 0.621 0.43 1.34E−25 Erbb2ip 5.61E−30 0.255253663 0.561 0.364 1.39E−25 BC005537 5.73E−30 0.286873064 0.611 0.45 1.42E−25 Aldh6a1 7.19E−30 0.266896818 0.829 0.704 1.78E−25 Gstm3 7.39E−30 −0.566844134 0.23 0.414 1.83E−25 Cd1d1 7.83E−30 0.269180487 0.747 0.612 1.95E−25 Hsd3b7 1.45E−29 −0.328539206 0.729 0.798 3.61E−25 Ppib 1.51E−29 −0.35186504 0.696 0.767 3.75E−25 Pigr 2.93E−29 0.275356693 0.957 0.947 7.29E−25 Baat 3.16E−29 0.262488362 0.862 0.767 7.84E−25 Pdk1 3.33E−29 0.256134304 0.438 0.251 8.28E−25 Atf5 6.07E−29 0.27075899 0.745 0.641 1.51E−24 Mup1 6.60E−29 −0.613763846 0.419 0.583 1.64E−24 Pipox 8.09E−29 0.267912272 0.69 0.549 2.01E−24 Sparcl1 1.50E−28 −0.253616986 0 0.136 3.72E−24 Sc4mol 2.00E−28 0.281384033 0.781 0.642 4.97E−24 Ptplad1 2.88E−28 0.278296625 0.654 0.496 7.14E−24 C8a 5.17E−28 −0.294138173 0.867 0.887 1.28E−23 Lrrc58 6.92E−28 0.264060967 0.543 0.359 1.72E−23 Actn4 7.75E−28 0.260860094 0.6 0.425 1.92E−23 Nfib 1.61E−27 0.250093732 0.55 0.364 4.00E−23 Maob 2.53E−27 0.272235996 0.708 0.575 6.28E−23 Apol7a 4.08E−27 0.271621562 0.559 0.382 1.01E−22 Ces1e 5.81E−27 0.294372509 0.71 0.576 1.44E−22 Hmgcs1 7.34E−27 0.296651807 0.858 0.703 1.82E−22 Fmo1 8.35E−27 0.263993508 0.606 0.415 2.07E−22 Ppm1a 1.41E−26 0.275992744 0.571 0.39 3.49E−22 Ptp4a2 1.73E−26 0.258986528 0.691 0.547 4.29E−22 Sh3glb1 2.26E−26 0.253791572 0.433 0.258 5.62E−22 Ttc39c 2.27E−26 −0.350463351 0.546 0.642 5.63E−22 Gm4076 3.58E−26 −0.301057344 0.035 0.184 8.88E−22 Uroc1 3.89E−26 0.307355817 0.726 0.615 9.66E−22 Mt2 9.21E−26 0.313597451 0.548 0.365 2.29E−21 Pdia6 1.14E−25 −0.335875757 0.611 0.712 2.82E−21 Iqgap2 3.16E−25 0.264494476 0.799 0.677 7.85E−21 Ptprd 6.32E−25 0.271860854 0.582 0.42 1.57E−20 0610007P14Rik 8.28E−25 0.251927159 0.512 0.346 2.06E−20 Ubr3 2.90E−24 0.252873563 0.585 0.41 7.20E−20 Mup13 6.00E−24 −0.469138263 0.418 0.546 1.49E−19 Upp2 1.76E−23 −0.285897303 0.545 0.673 4.36E−19 8430408G22Rik 2.02E−23 0.252689739 0.559 0.392 5.03E−19 Ppap2b 2.66E−23 0.257285533 0.593 0.43 6.61E−19 Cfhr2 6.41E−23 −0.303339186 0.885 0.868 1.59E−18 Hsd17b2 1.28E−22 −0.300549533 0.614 0.711 3.19E−18 Ifitm3 1.30E−22 −0.279693974 0.742 0.812 3.22E−18 Atp2a2 2.79E−22 0.253693334 0.64 0.495 6.92E−18 Mup2 1.19E−20 −0.500849516 0.256 0.392 2.96E−16 Hsd3b3 1.32E−20 −0.313033598 0.499 0.605 3.27E−16 Pnpla7 1.51E−20 −0.339749669 0.455 0.572 3.74E−16 Serp1 2.63E−20 −0.299204955 0.671 0.721 6.53E−16 Naa50 2.84E−20 0.265808764 0.517 0.358 7.04E−16 Eef1b2 4.19E−20 −0.268563341 0.743 0.78 1.04E−15 Cyp2e1 6.55E−20 0.347156447 0.93 0.911 1.63E−15 Fos 8.58E−20 0.327248556 0.619 0.51 2.13E−15 Cyp2c70 2.06E−19 −0.278293267 0.828 0.834 5.10E−15 Prdx4 6.87E−19 −0.313999267 0.517 0.607 1.71E−14 Rarres1 1.14E−18 −0.287428253 0.274 0.42 2.83E−14 Cyp7a1 3.08E−18 0.274384618 0.398 0.259 7.66E−14 Csad 4.37E−18 0.290595078 0.843 0.744 1.09E−13 Etnppl 4.63E−18 0.407010453 0.677 0.606 1.15E−13 Malat1 2.80E−17 −0.464666369 0.702 0.78 6.96E−13 Mup4 3.09E−17 −0.693444431 0.824 0.898 7.68E−13 Psmb1 3.10E−17 −0.265941959 0.703 0.759 7.70E−13 Rgn 3.36E−17 0.261419562 0.899 0.874 8.33E−13 Ndufb11 4.01E−17 −0.283194323 0.669 0.735 9.96E−13 Krt8 8.75E−16 −0.265010151 0.47 0.578 2.17E−11 Rpl32 3.29E−14 −0.263090496 0.689 0.757 8.17E−10 Cyp2c37 9.91E−14 0.289653212 0.71 0.608 2.46E−09 Selk 1.39E−13 −0.264704833 0.393 0.486 3.45E−09 Psmb5 2.01E−13 −0.263312926 0.241 0.348 4.98E−09 Ifi27 3.66E−13 −0.25720865 0.325 0.453 9.08E−09 Nme1 3.82E−13 −0.272417976 0.561 0.622 9.49E−09 Hes6 4.04E−13 −0.278057796 0.33 0.42 1.00E−08 Rps8 1.24E−12 −0.258468642 0.378 0.471 3.08E−08 Ubb 3.02E−08 −0.268532383 0.379 0.45 0.000750415 Rps15 5.07E−08 −0.254504371 0.468 0.528 0.001260068 Hsd17b13 5.79E−07 0.267753182 0.755 0.74 0.014383233 mmu-mir-6236 1.15E−06 −0.627231332 0.801 0.837 0.028554582 Oat 2.03E−05 0.343909058 0.653 0.611 0.504812214 Ftl1 2.40E−05 −0.279770666 0.363 0.409 0.597068016 mt-Atp6 0.000145832 −0.39551085 0.43 0.452 1 Gm20594 0.001254387 −0.292751004 0.262 0.294 1 Rpl41 0.062445139 −0.2575003 0.274 0.278 1

TABLE 5a Differentially expressed genes between time point PHX3 FC.1 and untreated (UT). p_val avg_logFC pct.1 pct.2 p_val_adj Saa2 0 2.971862499 0.999 0.222 0 Mt1 0 2.610854994 1 0.556 0 Mt2 0 2.6060431 1 0.365 0 Saa1 0 2.202156726 1 0.662 0 Steap4 0 1.890015167 0.973 0.222 0 Serpina3n 0 1.759758939 0.992 0.574 0 Lcn2 0 1.499141183 0.815 0.07 0 Lpin1 0 1.327657625 0.94 0.31 0 n-R5-8s1 0 1.289598504 0.805 0.031 0 Igfbp1 0 1.288789902 0.99 0.717 0 Cxcl1 0 1.230398019 0.919 0.314 0 Scd1 0 1.081676999 0.998 0.901 0 Gm26924 0 1.063463323 1 1 0 Il1r1 0 0.998168131 0.8 0.167 0 Fga 0 0.981249724 1 0.997 0 Gm24601 0 0.924568273 0.661 0.015 0 Nnmt 0 0.901052904 0.97 0.716 0 Itih4 0 0.887186241 0.999 0.948 0 St3gal5 0 0.882761517 0.915 0.49 0 Tacc2 0 0.877623973 0.707 0.071 0 Lrg1 0 0.870250525 0.981 0.736 0 Fam134b 0 0.865578177 0.876 0.405 0 Tat 0 0.857965136 0.998 0.903 0 Saa4 0 0.854921603 0.981 0.749 0 Thrsp 0 0.836598219 0.98 0.627 0 Slc39a14 0 0.831584936 0.849 0.343 0 Lars2 0 0.816795688 1 0.994 0 Fgg 0 0.809322713 1 0.991 0 Slc38a2 0 0.797899442 0.874 0.413 0 Serpina3m 0 0.779052745 0.961 0.722 0 Hp 0 0.774785279 1 0.999 0 Fgb 0 0.739519125 1 1 0 Gm15564 0 0.735157137 0.999 0.956 0 Serpina10 0 0.733655099 0.934 0.641 0 Plin2 0 0.720463076 0.952 0.714 0 Aass 0 0.705615345 0.965 0.716 0 Fmo5 0 0.690160801 0.991 0.837 0 Fn1 0 0.684266092 0.983 0.821 0 Fkbp5 0 0.663304836 0.665 0.117 0 Slc25a47 0 0.635928777 0.994 0.927 0 Mat1a 0 0.623734998 0.999 0.966 0 Aldob 0 0.490200848 1 0.996 0 Mup3 0 −0.526410044 1 1 0 Cyb5 0 −0.71965743 0.992 0.983 0 mt-Rnr1 0 −0.872186844 1 1 0 mt-Rnr2 0 −0.873557854 1 1 0 Mup11 0 −0.976755523 0.996 1 0 mt-Nd2 0 −1.128776891 0.996 0.999 0 mt-Nd1 0 −1.136736863 0.999 1 0 mt-Nd5 0 −1.145550707 0.974 0.995 0 mt-Co3 0 −1.233961828 0.106 0.603 0 Gm13775 0 −1.255657303 0.205 0.761 0 mt-Cytb 0 −1.296043506 0.993 0.999 0 mt-Co2 0 −1.341686736 0.1 0.629 0 mt-Co1 0 −1.381307687 0.986 0.999 0 mt-Nd4 0 −1.630375247 0.977 0.998 0 Mup4 0 −1.805301681 0.374 0.898 0 Mup6 0 −2.386597202 0.714 0.992 0 Mup9 0 −2.453596744 0.401 0.976 0 Mup17 0 −2.514472885 0.899 1 0 Mup18 0 −2.617739049 0.547 0.997 0 Mup19 0 −2.932276479 0.84 1 0 Acox1 2.96439387504748e−323 0.540022158 0.998 0.966  7.3611828705179e−319 Hnf4a 1.23516411460312e−322 0.644195253 0.969 0.743 3.06715952938246e−318 B3galt1 2.95451256213065e−321 0.788734938 0.634 0.163 7.33664559428284e−317 Cyp2b10 3.42189866309647e−320 −1.254972098 0.132 0.542 8.49725876020116e−316 Mup5 5.13739339858645e−319 −1.484560547 0.52 0.839 1.27571752873699e−314 H3f3b 1.54603021896643e−318 0.755567107 0.831 0.419 3.83910223973744e−314 Btg2 0.00E+00 0.772686832 0.708 0.241  2.89E−305 Sephs2 0.00E+00 0.618707003 0.974 0.761  3.26E−305 Ankrd55  1.93E−296 −1.464696038 0.374 0.696  4.78E−292 Hspb8  2.89E−295 0.667847253 0.914 0.597  7.19E−291 Slc7a2  8.07E−288 0.622326529 0.964 0.735  2.01E−283 Cldn14  1.24E−283 0.511583526 0.505 0.076  3.09E−279 C3  8.73E−282 0.482674202 0.999 0.99  2.17E−277 Gjb2  1.09E−277 0.639507436 0.901 0.572  2.70E−273 Rcan1  1.31E−277 0.509239866 0.522 0.085  3.25E−273 Errfi1  1.31E−267 0.500850526 0.998 0.911  3.25E−263 Pfkfb3  1.05E−265 0.426580733 0.421 0.039  2.60E−261 Arhgef26  1.83E−264 0.568544702 0.67 0.203  4.56E−260 Cyp2c29  3.96E−262 −1.027267705 0.751 0.93  9.83E−258 Egfr  1.26E−254 0.555834247 0.989 0.809  3.12E−250 Gsta3  1.87E−250 −0.53784222 0.993 0.956  4.64E−246 Bcl3  1.73E−248 0.419650143 0.479 0.074  4.30E−244 Snx10  3.96E−247 0.558244633 0.63 0.188  9.84E−243 Pck1  1.36E−246 0.43447474 0.999 0.987  3.37E−242 Mup16  4.33E−246 −0.848726713 0.816 0.934  1.07E−241 Bach1  1.17E−243 0.533237374 0.589 0.151  2.91E−239 Tifa  8.59E−243 0.392339477 0.393 0.036  2.13E−238 Hpx  1.42E−241 0.460272423 1 0.997  3.52E−237 Ugt2b5  1.30E−240 −0.423085187 0.991 0.959  3.23E−236 Etnk2  3.72E−240 0.592353201 0.918 0.655  9.25E−236 2010003K11Rik  8.42E−239 0.372219971 0.412 0.046  2.09E−234 Rapgef4  1.08E−237 0.588317735 0.836 0.436  2.69E−233 Tiparp  5.34E−233 0.489122153 0.485 0.087  1.33E−228 Gpt2  4.65E−230 0.533331785 0.949 0.725  1.15E−225 Slc25a25  1.00E−226 0.544465891 0.945 0.704  2.48E−222 Mup10  7.92E−224 0.428268029 0.965 0.692  1.97E−219 Txnip  3.60E−223 0.552612237 0.741 0.297  8.94E−219 Cyp2c50  1.21E−219 −0.763912176 0.693 0.888  3.02E−215 Xbp1  4.00E−219 0.539986 0.89 0.57  9.93E−215 Upp2  6.55E−218 0.541753512 0.934 0.673  1.63E−213 Mfsd2a  1.62E−217 0.496351884 0.563 0.148  4.02E−213 Ephb3  4.02E−217 0.188403248 0.244 0.001  9.97E−213 Actb  2.92E−216 0.456981443 0.99 0.886  7.25E−212 mmu-mir-6236  7.87E−215 0.468866739 0.989 0.837  1.95E−210 Fbf1  1.44E−212 0.298573909 0.336 0.027  3.58E−208 Trib1  3.58E−209 0.581754281 0.705 0.308  8.89E−205 Hsd3b5  4.49E−209 −0.587528886 0.49 0.587  1.12E−204 Arg1  8.68E−205 0.381616351 1 0.982  2.16E−200 Plin5  3.05E−204 0.489257529 0.736 0.315  7.56E−200 Plk3  5.05E−204 0.488016367 0.644 0.226  1.26E−199 Mup13  2.17E−203 −0.755608269 0.303 0.546  5.38E−199 Mtss1  7.69E−203 0.552137981 0.812 0.454  1.91E−198 Klf6  1.10E−202 0.3616937 0.346 0.034  2.74E−198 Itih3  1.01E−201 0.469631651 0.988 0.89  2.51E−197 Gm23935  3.69E−201 0.498066925 0.999 0.925  9.17E−197 Mup21  3.26E−199 −0.668770594 0.829 0.929  8.09E−195 Adck3  1.22E−198 −0.482940158 0.729 0.764  3.02E−194 Cyp2c54  5.69E−198 −0.712859584 0.491 0.759  1.41E−193 Slc10a2  2.81E−196 0.30563824 0.376 0.05  6.99E−192 Egr1  4.80E−196 0.620480469 0.79 0.447  1.19E−191 Sdc4  5.23E−196 0.43560504 0.986 0.867  1.30E−191 Serpina3c  5.27E−196 −0.554657351 0.118 0.385  1.31E−191 Apcs  5.83E−195 0.573439593 0.854 0.525  1.45E−190 Atf3  1.04E−193 0.597274889 0.56 0.179  2.59E−189 Hsd3b7  2.55E−191 −0.451728474 0.795 0.798  6.34E−187 Orm1  4.40E−190 0.463411533 0.993 0.952  1.09E−185 Glul  9.28E−190 0.478908893 0.58 0.18  2.30E−185 Pzp  1.11E−189 0.387351113 0.999 0.986  2.75E−185 Prg4  7.24E−189 0.480504574 0.585 0.188  1.80E−184 Fgl1  2.00E−188 0.49338252 0.961 0.784  4.97E−184 Gpcpd1  4.07E−188 0.53780646 0.778 0.398  1.01E−183 Klf10  5.00E−188 0.304779554 0.388 0.06  1.24E−183 Rgs16  2.31E−187 0.438105488 0.482 0.113  5.72E−183 Ptp4a1  3.32E−187 0.393137367 0.528 0.145  8.25E−183 mt-Atp6  3.88E−186 −0.852555757 0.138 0.452  9.63E−182 Fam35a  2.55E−184 0.470461753 0.642 0.246  6.34E−180 Rhob  2.99E−184 0.37207281 0.4 0.069  7.42E−180 Mup15  8.65E−184 −1.074409915 0.357 0.617  2.15E−179 Cyp3a25  1.35E−183 −0.41051207 0.928 0.919  3.35E−179 Got1  2.81E−183 0.542891511 0.866 0.587  6.99E−179 Ces1d  1.16E−179 −0.385155368 0.944 0.923  2.88E−175 Shb  1.22E−178 0.430613558 0.589 0.204  3.02E−174 Sds  6.42E−177 0.787094904 0.868 0.67  1.59E−172 Abca1  4.57E−176 0.50506234 0.756 0.377  1.14E−171 1810055G02Rik  7.51E−174 0.382584093 0.528 0.155  1.86E−169 Stat3  1.08E−172 0.460515229 0.701 0.318  2.69E−168 Akr1c6  4.37E−171 −0.43492211 0.992 0.971  1.08E−166 Apoe  2.24E−170 −0.26209828 1 1  5.55E−166 Igfbp4  5.75E−170 0.387861679 0.986 0.866  1.43E−165 Cdkn1a  2.80E−169 0.449325471 0.572 0.195  6.96E−165 Gfra1  6.66E−169 0.474694426 0.835 0.498  1.65E−164 Gc  2.58E−168 0.233764264 1 0.999  6.42E−164 Nrg4  3.51E−168 0.246089001 0.306 0.034  8.72E−164 Ivns1abp  1.57E−166 0.46254094 0.688 0.315  3.89E−162 Fh1  2.76E−165 0.471428771 0.915 0.648  6.86E−161 Myo1e  9.09E−164 0.399456672 0.551 0.182  2.26E−159 Slc41a2  1.23E−163 0.3685439 0.482 0.134  3.04E−159 Mup8  2.63E−163 −0.793731191 0.111 0.373  6.53E−159 Slc25a51  3.37E−163 0.372157664 0.522 0.161  8.37E−159 Psen2  3.10E−162 −0.419555606 0.749 0.774  7.69E−158 Dak  4.15E−162 0.481947664 0.867 0.563  1.03E−157 Apoc4  4.45E−160 −0.356086407 0.999 0.98  1.10E−155 Arid5a  1.22E−159 0.163384737 0.208 0.005  3.03E−155 Fasn  1.97E−159 0.467168076 0.719 0.345  4.89E−155 Bhlhe40  9.52E−159 0.403249298 0.628 0.251  2.36E−154 Tmem87b  4.61E−156 0.288330587 0.415 0.096  1.15E−151 Ddx3x  2.02E−155 0.47100162 0.823 0.513  5.01E−151 Ttr  3.46E−155 0.248320061 1 1  8.59E−151 Aldh1a1  9.02E−152 −0.40245097 0.984 0.956  2.24E−147 Slc25a22  2.27E−151 0.390931532 0.649 0.282  5.65E−147 Rnf103  9.68E−150 0.438540394 0.701 0.35  2.40E−145 Scara5  1.84E−149 0.221632911 0.324 0.054  4.57E−145 B4galt1  3.68E−147 0.321380868 0.494 0.155  9.13E−143 Hacl1  1.79E−146 −0.332899987 0.842 0.797  4.44E−142 Rnf125  2.78E−146 −0.463320018 0.312 0.493  6.90E−142 Gm26917  2.01E−145 0.46739621 0.523 0.181  4.98E−141 Junb  2.83E−145 0.458500682 0.788 0.47  7.03E−141 Cps1  5.10E−145 0.336429448 0.999 0.971  1.27E−140 Atp1b1  2.13E−144 0.424801231 0.567 0.226  5.28E−140 Glud1  8.86E−144 0.341724783 0.991 0.905  2.20E−139 D10Wsu102e  2.68E−142 0.256022156 0.338 0.063  6.64E−138 Hyou1  3.20E−142 0.431109873 0.731 0.385  7.93E−138 Jmjd1c  3.24E−142 0.39612601 0.516 0.178  8.04E−138 4933426M11Rik  8.78E−142 0.28624304 0.419 0.109  2.18E−137 Apoa5  9.82E−142 0.30259839 0.999 0.974  2.44E−137 Scp2  5.80E−141 0.279911381 0.997 0.986  1.44E−136 Jun  2.39E−140 0.479246114 0.864 0.593  5.93E−136 Cyp2a5  4.56E−140 −0.938183249 0.278 0.555  1.13E−135 Mup12  4.71E−140 −0.589618573 0.792 0.86  1.17E−135 Cpt1a  8.94E−140 0.42860734 0.894 0.651  2.22E−135 Pik3r1  1.33E−139 0.389193614 0.577 0.231  3.30E−135 Apob  5.29E−139 0.416824707 0.997 0.989  1.31E−134 Hmox1  1.29E−137 0.169723562 0.22 0.016  3.21E−133 Epas1  1.76E−136 0.38425941 0.646 0.297  4.38E−132 Ugt2b36  9.83E−136 −0.287193139 0.978 0.93  2.44E−131 Mbd1  2.08E−135 0.348094524 0.507 0.176  5.16E−131 Mup2  8.39E−135 −0.650107006 0.161 0.392  2.08E−130 Pik3ap1  9.99E−135 0.19440062 0.283 0.043  2.48E−130 Foxq1  5.85E−134 0.22551931 0.377 0.096  1.45E−129 Slc22a5  9.36E−134 0.185456618 0.32 0.065  2.32E−129 Gadd45g  2.40E−133 0.392031882 0.899 0.639  5.96E−129 Bcl2l1  6.34E−133 0.280315334 0.426 0.122  1.57E−128 Fos  6.58E−133 0.524733327 0.785 0.51  1.63E−128 Ptpn1  8.98E−133 0.268263225 0.402 0.107  2.23E−128 Slc25a15  2.35E−132 0.402049896 0.931 0.738  5.83E−128 Tdo2  9.76E−132 0.25156007 0.999 0.991  2.42E−127 Rnd3  2.07E−131 0.285147682 0.375 0.091  5.13E−127 Adh1  3.50E−131 −0.295980789 0.995 0.96  8.69E−127 Litaf  6.42E−131 0.396007707 0.603 0.278  1.59E−126 Gm5096  1.40E−130 −0.399548106 0.364 0.468  3.47E−126 Wbp1l  9.53E−130 0.409138156 0.867 0.606  2.37E−125 Grn  5.30E−129 0.403315761 0.726 0.396  1.32E−124 Tns1  6.02E−129 0.33981795 0.524 0.196  1.50E−124 Cyp2c37  7.90E−129 −0.662335734 0.314 0.608  1.96E−124 Ahcy  1.61E−128 −0.375627724 0.918 0.916  4.01E−124 Foxa3  4.51E−128 0.307992015 0.505 0.182  1.12E−123 Qsox1  7.12E−128 0.378486857 0.925 0.707  1.77E−123 Cth  1.21E−127 −0.308847665 0.898 0.838  3.00E−123 Id2  3.26E−127 0.430147785 0.826 0.579  8.09E−123 1700017B05Rik  7.08E−127 0.182766029 0.263 0.037  1.76E−122 Myh9  9.38E−127 0.399128031 0.653 0.318  2.33E−122 Cox6c  7.06E−126 −0.41128283 0.893 0.884  1.75E−121 Raph1  3.03E−125 0.242670968 0.382 0.1  7.52E−121 Ier2  5.55E−123 0.452598264 0.763 0.49  1.38E−118 Cfh  6.71E−123 0.312615767 0.991 0.897  1.67E−118 Itih2  1.73E−122 0.336714211 0.984 0.884  4.30E−118 Ccnl1  1.52E−121 0.341338448 0.526 0.206  3.77E−117 Rsp14  1.65E−121 −0.346340977 0.936 0.917  4.10E−117 Cyp8b1  2.36E−121 −0.364571013 0.714 0.745  5.87E−117 Cox4i1  2.43E−121 −0.288035158 0.992 0.958  6.04E−117 Eef1a1  6.76E−121 0.340768186 0.967 0.85  1.68E−116 Nedd4l  2.66E−120 0.271827098 0.447 0.147  6.62E−116 Inmt  6.92E−120 −0.308364158 0.966 0.884  1.72E−115 Slc37a1  1.40E−119 0.133887938 0.198 0.015  3.49E−115 Cep85l  1.73E−119 0.202664771 0.347 0.089  4.29E−115 Elovl5  6.66E−119 0.382267188 0.863 0.58  1.65E−114 Zbtb16  7.66E−119 0.232600907 0.414 0.131  1.90E−114 Il17ra  3.02E−118 0.203529938 0.302 0.061  7.51E−114 Hip1r  3.74E−118 0.213858215 0.362 0.098  9.27E−114 Gcc1  5.57E−118 0.175053461 0.258 0.04  1.38E−113 Plg  5.78E−118 0.26619661 0.998 0.961  1.43E−113 Eif4g2  8.12E−118 0.384302798 0.905 0.678  2.02E−113 Atg14  1.14E−117 0.231648357 0.369 0.1  2.83E−113 Ppip5k2  1.68E−117 0.30299148 0.51 0.197  4.16E−113 Ulk1  3.53E−117 0.297841785 0.499 0.189  8.77E−113 Elovl6  1.30E−116 0.37962641 0.553 0.24  3.24E−112 Pon1  1.35E−116 −0.302819466 0.936 0.906  3.35E−112 Il6ra  6.12E−116 0.251696836 0.431 0.142  1.52E−111 Adamts1  3.82E−115 0.15752777 0.202 0.018  9.49E−111 Ndufb11  7.95E−115 −0.36792318 0.722 0.735  1.97E−110 Ets2  1.01E−113 0.183062901 0.285 0.056  2.50E−109 Igfbp2  4.23E−113 −0.348403589 0.886 0.885  1.05E−108 Fads2  1.77E−112 0.323744791 0.592 0.273  4.40E−108 Tnfrsf1a  2.83E−112 0.346845029 0.551 0.244  7.02E−108 Gcnt2  3.56E−112 0.221618104 0.333 0.082  8.85E−108 Ugt2b34  4.78E−112 −0.290735843 0.918 0.874  1.19E−107 Ell2  5.81E−112 0.371745977 0.72 0.416  1.44E−107 Ly6e  6.33E−112 0.42022985 0.68 0.386  1.57E−107 Rps2  1.81E−110 −0.44250848 0.675 0.757  4.49E−106 Epb4.1  3.41E−110 0.349430673 0.617 0.304  8.48E−106 Dscr3  6.96E−110 0.180232898 0.339 0.09  1.73E−105 Ptpn2  1.69E−109 0.225408583 0.354 0.097  4.20E−105 Zc3h13  9.21E−109 0.204542393 0.325 0.083  2.29E−104 Clpx  1.01E−108 −0.306093278 0.818 0.783  2.51E−104 Rps27l  5.04E−108 −0.361138678 0.855 0.849  1.25E−103 Dst  5.40E−108 0.329905553 0.507 0.206  1.34E−103 Atl2  1.09E−107 0.321873809 0.674 0.361  2.72E−103 Gm4076  1.71E−107 −0.342157966 0.007 0.184  4.24E−103 Lpgat1  3.04E−107 0.390146943 0.776 0.502  7.54E−103 Gm20594  3.81E−107 −0.559577825 0.108 0.294  9.47E−103 Slc41a1  7.08E−107 0.110049944 0.168 0.011  1.76E−102 Hmgcs1  8.42E−107 −0.258009688 0.778 0.703  2.09E−102 Esd  2.48E−106 −0.302906103 0.794 0.784  6.15E−102 Oaz1  3.13E−106 −0.339004868 0.759 0.75  7.77E−102 Pptc7  8.30E−106 0.227095018 0.412 0.141  2.06E−101 Sult1a1  1.33E−105 0.371023537 0.899 0.707  3.29E−101 Ctif  2.36E−105 0.18604392 0.312 0.078  5.85E−101 Nfil3  2.49E−105 0.338730712 0.617 0.309  6.19E−101 Gpx1  6.46E−105 −0.222094695 1 0.999  1.60E−100 Cyp3a11  6.66E−105 −0.251219977 0.999 1  1.65E−100 Aqp8  7.56E−105 −0.331182913 0.444 0.505  1.88E−100 Socs3  1.67E−104 0.194515821 0.456 0.183  4.14E−100 Srrm4  2.29E−104 0.117065188 0.195 0.021  5.69E−100 Apoa4  2.82E−104 0.609214916 0.604 0.339  7.01E−100 Cml1  3.26E−104 −0.277339974 0.803 0.757  8.09E−100 Jak1  3.38E−104 0.362766687 0.648 0.342  8.40E−100 Arid5b  4.92E−104 0.232391653 0.472 0.186 1.22E−99 Rasgef1b  7.14E−104 0.174426927 0.279 0.06 1.77E−99 Cers6  8.32E−104 0.1318056 0.198 0.022 2.07E−99 Baiap2l1  9.30E−104 0.187103281 0.395 0.136 2.31E−99 Rrs1  1.41E−103 0.167967739 0.314 0.082 3.51E−99 Ralgapa2  2.43E−103 0.20791298 0.334 0.092 6.04E−99 G6pc  4.74E−103 0.341403933 0.948 0.752 1.18E−98 Rlf  7.11E−103 0.176204022 0.321 0.086 1.76E−98 Ifitm3  2.36E−102 0.331673739 0.958 0.812 5.86E−98 Zfp36  2.64E−102 0.407014847 0.776 0.522 6.55E−98 Oaf  7.72E−102 −0.333766768 0.79 0.794 1.92E−97 Mgst1  7.79E−102 −0.322742924 1 0.997 1.93E−97 Uqcrq  1.17E−101 −0.316451873 0.98 0.951 2.90E−97 Garem  4.69E−101 0.204881738 0.351 0.104 1.16E−96 B2m  6.16E−101 0.246889569 0.997 0.963 1.53E−96 Man2a1  4.39E−100 0.369999358 0.83 0.583 1.09E−95 Hebp1  4.64E−100 −0.313009472 0.742 0.75 1.15E−95 Sod1  5.22E−100 −0.238388169 0.998 0.983 1.30E−95 mt-Nd6  7.05E−100 −0.515107457 0.389 0.577 1.75E−95 Map3k5  9.85E−100 0.21643947 0.411 0.147 2.45E−95 Hint2 1.16E−99 −0.299309844 0.685 0.676 2.87E−95 Ndufb6 1.92E−99 −0.311202811 0.77 0.759 4.76E−95 Palmd 2.20E−99 0.284673594 0.51 0.219 5.47E−95 Eef2 2.93E−99 0.289562847 0.979 0.873 7.28E−95 3110043O21Rik 3.71E−99 0.171966272 0.282 0.065 9.20E−95 Heatr1 4.46E−99 0.163145002 0.275 0.062 1.11E−94 Mgll 8.84E−99 0.321840174 0.739 0.449 2.19E−94 Vtn 1.05E−98 0.225160672 0.999 0.983 2.62E−94 Aff4 3.03E−98 0.344186222 0.635 0.337 7.53E−94 Pawr 3.27E−98 0.116243505 0.217 0.035 8.13E−94 Aldh1l1 6.75E−98 0.277372649 0.991 0.904 1.68E−93 Tef 7.02E−98 0.127953279 0.384 0.148 1.74E−93 Wdr45b 7.39E−98 0.246836045 0.459 0.181 1.83E−93 Kdm4a 1.53E−97 0.172058145 0.3 0.077 3.79E−93 Gpd2 4.49E−97 0.23284812 0.393 0.135 1.12E−92 Atp2a2 5.99E−97 0.350363266 0.771 0.495 1.49E−92 Gadd45a 2.39E−96 0.231268974 0.41 0.149 5.93E−92 Mbnl2 3.18E−96 0.249293642 0.444 0.172 7.90E−92 Eif1a 3.51E−96 0.295219945 0.583 0.289 8.73E−92 Igf1 5.12E−96 0.277138761 0.989 0.904 1.27E−91 Acaa1b 5.53E−96 −0.263859024 0.968 0.969 1.37E−91 Slc30a5 6.62E−96 0.207315427 0.378 0.126 1.65E−91 Cyb5r3 1.40E−95 0.337684684 0.906 0.725 3.49E−91 Il13ra1 1.49E−95 0.214635625 0.402 0.143 3.69E−91 Dopey2 3.36E−95 0.19521799 0.33 0.097 8.35E−91 Trak2 4.32E−95 0.13630483 0.264 0.062 1.07E−90 Slc3a1 8.69E−95 0.290117272 0.464 0.189 2.16E−90 Nop58 2.05E−94 0.257566653 0.428 0.162 5.10E−90 Ttpal 2.08E−94 0.129043255 0.243 0.051 5.15E−90 Serpina1e 2.45E−94 0.233787997 1 0.999 6.07E−90 Gm2a 3.18E−94 0.341145926 0.704 0.427 7.89E−90 Ell 4.24E−94 0.161665745 0.291 0.076 1.05E−89 Por 5.25E−94 0.290745567 0.898 0.675 1.30E−89 Mvd 5.90E−94 −0.327327327 0.085 0.269 1.47E−89 Sparcl1 7.09E−94 −0.253616986 0 0.136 1.76E−89 Rpl13a 3.14E−93 −0.314606263 0.858 0.868 7.80E−89 Enpp2 5.14E−93 0.316882991 0.635 0.345 1.28E−88 Kng1 6.56E−93 0.194558698 1 0.991 1.63E−88 Mpc2 6.72E−93 −0.268047152 0.887 0.857 1.67E−88 Cep110 8.04E−93 0.192096419 0.362 0.121 2.00E−88 Creb3l2 1.67E−92 0.161215013 0.278 0.068 4.14E−88 Ambp 2.13E−92 0.211238054 0.999 0.993 5.28E−88 Dstn 2.99E−92 0.271381717 0.664 0.37 7.44E−88 Cyp1a2 3.17E−92 −0.481919967 0.685 0.794 7.86E−88 Pfkfb2 1.80E−91 0.160198891 0.27 0.067 4.47E−87 Ahsg 1.83E−91 0.171853168 1 1 4.55E−87 Sec14l4 1.91E−91 0.285169227 0.724 0.436 4.74E−87 Slc38a3 4.51E−91 0.292400046 0.971 0.858 1.12E−86 Xdh 1.64E−90 0.27224472 0.541 0.258 4.08E−86 Cfhr2 2.62E−90 −0.246923339 0.949 0.868 6.51E−86 Slc16a6 3.77E−90 0.21530975 0.251 0.054 9.35E−86 Spin1 4.11E−90 0.232119983 0.478 0.206 1.02E−85 Coq10b 6.51E−90 0.153862213 0.313 0.093 1.62E−85 Dusp1 1.08E−89 0.300628481 0.539 0.259 2.67E−85 Ubc 2.12E−89 −0.273242853 0.907 0.872 5.27E−85 Aadac 3.37E−89 −0.230855362 0.952 0.86 8.37E−85 Txnrd1 3.83E−89 0.314979852 0.721 0.441 9.50E−85 Serinc3 1.76E−88 0.293964974 0.713 0.433 4.36E−84 Slc20a1 2.48E−88 0.125755272 0.279 0.076 6.17E−84 Dbi 2.79E−88 0.243173797 0.999 0.971 6.93E−84 C8a 5.37E−88 0.294064237 0.978 0.887 1.33E−83 Eci2 1.87E−87 0.288159513 0.896 0.698 4.64E−83 Chd1 1.92E−87 0.213257509 0.42 0.166 4.77E−83 Elovl2 2.69E−87 0.285038606 0.912 0.699 6.69E−83 Atf6 2.82E−87 0.280521162 0.553 0.273 6.99E−83 Lrp6 3.24E−87 0.270740438 0.505 0.232 8.05E−83 Maff 9.72E−87 0.118590539 0.222 0.048 2.41E−82 Nr4a1 1.19E−86 0.13631399 0.207 0.036 2.96E−82 Myo18a 4.19E−86 0.233717966 0.476 0.211 1.04E−81 Sigmar1 6.27E−86 −0.282364617 0.482 0.514 1.56E−81 Gck 6.72E−86 0.260705425 0.557 0.278 1.67E−81 D5Ertd579e 7.81E−86 0.197825601 0.328 0.104 1.94E−81 Creg1 9.18E−86 −0.235698597 0.966 0.926 2.28E−81 Tnfrsf12a 1.24E−85 0.114819395 0.233 0.052 3.07E−81 D630036G22Rik 1.31E−85 0.147427696 0.268 0.071 3.25E−81 Atp5f1 1.90E−85 −0.217555876 0.943 0.869 4.71E−81 Zfp445 2.06E−85 0.159662672 0.371 0.138 5.12E−81 Id3 2.29E−85 0.399520373 0.688 0.426 5.68E−81 Ndufa6 2.67E−85 −0.25272382 0.846 0.798 6.62E−81 Nfkbiz 3.10E−85 0.157772695 0.249 0.059 7.69E−81 Kansl1 3.35E−85 0.146121195 0.286 0.08 8.31E−81 Asl 3.71E−85 0.297673772 0.934 0.787 9.22E−81 Tgm2 8.13E−85 0.316575272 0.524 0.258 2.02E−80 Cpb2 9.20E−85 0.280302458 0.959 0.813 2.28E−80 Uroc1 2.32E−84 0.329587334 0.837 0.615 5.77E−80 Aox3 2.71E−84 0.275388909 0.989 0.894 6.73E−80 Ddi2 3.48E−84 0.302519699 0.642 0.365 8.63E−80 Etv6 6.75E−84 0.143861801 0.266 0.069 1.68E−79 Aim1 6.84E−84 0.132131086 0.302 0.098 1.70E−79 Tsr1 7.09E−84 0.149561769 0.311 0.097 1.76E−79 Flnb 1.86E−83 0.212710481 0.376 0.139 4.61E−79 Rab30 2.08E−83 0.112636253 0.235 0.056 5.16E−79 Fgf1 2.27E−83 0.287983029 0.647 0.369 5.65E−79 Cobll1 3.65E−83 0.158603105 0.353 0.13 9.07E−79 Arl4d 4.26E−83 −0.328520283 0.326 0.437 1.06E−78 H6pd 1.81E−82 0.300492669 0.825 0.595 4.50E−78 Tsc22d2 2.10E−82 0.165988347 0.349 0.124 5.21E−78 Ddx5 6.27E−82 0.251675045 0.778 0.515 1.56E−77 Megf9 6.42E−82 0.211011671 0.401 0.158 1.59E−77 Ctsb 6.42E−82 0.268200419 0.943 0.781 1.60E−77 Il6st 7.72E−82 0.262348153 0.544 0.273 1.92E−77 Mttp 8.01E−82 0.296651415 0.888 0.697 1.99E−77 Orm2 9.10E−82 0.144101366 0.286 0.09 2.26E−77 Gde1 2.65E−81 0.222485647 0.531 0.263 6.58E−77 Gm9843 2.74E−81 −0.343302667 0.197 0.299 6.81E−77 Zfp36l2 3.05E−81 0.103487303 0.215 0.05 7.57E−77 Slc35g1 3.63E−81 0.166162728 0.36 0.133 9.02E−77 Trp53inp1 4.94E−81 0.269278401 0.582 0.308 1.23E−76 Rmnd5a 6.65E−81 0.273473023 0.628 0.352 1.65E−76 Fads1 7.20E−81 0.267264464 0.889 0.663 1.79E−76 Nrp1 1.23E−80 0.268796793 0.518 0.253 3.05E−76 Rbm47 1.73E−80 0.21054927 0.475 0.218 4.29E−76 Lrp1 1.82E−80 0.310226628 0.831 0.591 4.51E−76 Gm10250 1.89E−80 −0.30688429 0.124 0.251 4.69E−76 C4bp 2.56E−80 0.26668764 0.948 0.788 6.36E−76 Prox1 2.59E−80 0.31520499 0.622 0.351 6.44E−76 Cebpa 3.88E−80 −0.260692112 0.688 0.672 9.63E−76 Angptl4 3.88E−80 0.315315425 0.838 0.629 9.63E−76 Clip1 4.78E−80 0.166877376 0.438 0.196 1.19E−75 Cish 6.18E−80 0.172549219 0.302 0.093 1.53E−75 Lbp 1.00E−79 0.264248666 0.605 0.333 2.49E−75 Hs6st1 1.20E−79 0.206647988 0.524 0.261 2.99E−75 Zfp683 1.36E−79 −0.421689112 0 0.116 3.38E−75 Clu 1.66E−79 0.2220984 0.995 0.958 4.13E−75 Picalm 1.74E−79 0.276902165 0.648 0.376 4.32E−75 Acly 1.84E−79 0.287663867 0.715 0.445 4.57E−75 Cox7b 1.88E−79 −0.304638563 0.91 0.878 4.67E−75 Dcxr 1.93E−79 −0.271339616 0.629 0.631 4.79E−75 Myd88 2.01E−79 0.121633496 0.254 0.068 5.00E−75 Malat1 3.00E−79 −0.652623643 0.704 0.78 7.46E−75 Elovl3 5.41E−79 −0.25229278 0.838 0.827 1.34E−74 Hs3st3b1 1.01E−78 0.242350838 0.501 0.241 2.50E−74 Atp5h 1.29E−78 −0.351854327 0.688 0.682 3.20E−74 Ipo7 2.63E−78 0.176153152 0.402 0.168 6.52E−74 Nit2 2.92E−78 −0.196867848 0.62 0.577 7.24E−74 Casp8 2.93E−78 0.130902157 0.325 0.118 7.27E−74 Pdp2 3.49E−78 0.130918419 0.298 0.102 8.67E−74 Uox 4.04E−78 0.189986074 0.998 0.965 1.00E−73 Azin1 4.14E−78 0.268891169 0.59 0.322 1.03E−73 Tmed5 5.52E−78 0.296018777 0.74 0.492 1.37E−73 Ppp2r5a 6.09E−78 −0.263513608 0.593 0.594 1.51E−73 Lrrc16a 7.34E−78 0.127437209 0.244 0.063 1.82E−73 Tbl1xr1 8.85E−78 0.204315292 0.418 0.176 2.20E−73 Copa 1.43E−77 0.251410027 0.633 0.363 3.55E−73 Gm20721 1.75E−77 0.117268341 0.229 0.056 4.35E−73 Hist1h1c 2.20E−77 −0.331045753 0.24 0.372 5.47E−73 Gnl3 4.69E−77 0.242175469 0.454 0.204 1.16E−72 Bhmt 6.30E−77 −0.236483408 0.988 0.956 1.56E−72 Nr1d2 1.05E−76 0.159943118 0.411 0.179 2.61E−72 Sord 1.07E−76 −0.228716308 0.964 0.931 2.65E−72 mt-Tm 1.17E−76 0.126497553 0.283 0.093 2.91E−72 Rhobtb1 1.59E−76 0.178172942 0.406 0.172 3.94E−72 Ddhd2 1.79E−76 0.105524805 0.267 0.083 4.45E−72 Pik3c2a 2.23E−76 0.232920912 0.444 0.198 5.53E−72 Sec14l2 4.97E−76 −0.220330298 0.905 0.856 1.23E−71 Ythdc1 5.91E−76 0.15157378 0.369 0.15 1.47E−71 Smoc1 7.84E−76 0.212439914 0.49 0.238 1.95E−71 Plec 8.34E−76 0.197499812 0.424 0.186 2.07E−71 Pros1 8.47E−76 0.121465912 0.373 0.158 2.10E−71 Hipk3 1.03E−75 0.225614187 0.472 0.223 2.56E−71 Bag3 1.60E−75 0.187468684 0.376 0.148 3.97E−71 Ctsl 1.66E−75 0.256520866 0.976 0.857 4.11E−71 Ppib 1.75E−75 −0.223880669 0.823 0.767 4.33E−71 Suco 2.17E−75 0.112486448 0.307 0.113 5.39E−71 Angptl3 2.21E−75 −0.18094369 0.993 0.944 5.49E−71 Iqgap2 2.81E−75 0.283192936 0.879 0.677 6.97E−71 Hhex 3.00E−75 −0.283483187 0.229 0.307 7.46E−71 Acsl4 3.34E−75 0.250793464 0.588 0.323 8.30E−71 Nr1i2 4.43E−75 0.198788095 0.505 0.252 1.10E−70 Clp1 5.40E−75 0.153048593 0.307 0.103 1.34E−70 Ddc 9.70E−75 −0.216024433 0.475 0.46 2.41E−70 Lrpprc 1.15E−74 0.257016288 0.662 0.398 2.85E−70 Slc38a4 1.26E−74 0.244607846 0.976 0.877 3.13E−70 Sc4mol 1.49E−74 −0.23053256 0.669 0.642 3.71E−70 Lurap1l 1.62E−74 0.241965054 0.563 0.301 4.03E−70 Sik1 1.73E−74 0.111557849 0.257 0.078 4.31E−70 Akap11 2.07E−74 0.187807202 0.392 0.164 5.15E−70 Taf2 2.10E−74 0.146241085 0.25 0.067 5.21E−70 Cyp2c70 3.28E−74 0.25600888 0.971 0.834 8.15E−70 Lipg 3.43E−74 0.107109358 0.215 0.051 8.52E−70 Tirap 3.44E−74 0.131022584 0.304 0.106 8.54E−70 Gstp1 5.57E−74 0.197542109 0.962 0.822 1.38E−69 Spty2d1 6.27E−74 0.105732944 0.27 0.087 1.56E−69 Chd7 6.41E−74 0.135402444 0.27 0.085 1.59E−69 Sc5d 6.91E−74 −0.107743918 0.907 0.776 1.72E−69 Hsd3b3 7.80E−74 −0.226222481 0.631 0.605 1.94E−69 Sec24a 9.16E−74 0.188750112 0.504 0.255 2.28E−69 Csmp1 1.23E−73 0.127548152 0.319 0.122 3.05E−69 Sepp1 1.42E−73 0.16148927 1 1 3.51E−69 Gstm3 1.76E−73 −0.470077922 0.343 0.414 4.37E−69 Ass1 2.23E−73 0.216965784 0.996 0.962 5.55E−69 Cfi 2.41E−73 0.226479679 0.988 0.905 5.99E−69 Fbxo34 3.57E−73 0.143040285 0.301 0.104 8.86E−69 Ppp1r3b 5.81E−73 0.259418401 0.642 0.38 1.44E−68 Arhgef12 7.54E−73 0.280147378 0.667 0.408 1.87E−68 Usp9x 1.10E−72 0.233121474 0.556 0.299 2.73E−68 Rapgef2 1.13E−72 0.117395681 0.237 0.067 2.82E−68 Arnt 1.36E−72 0.102920838 0.212 0.052 3.38E−68 Fbxo31 1.45E−72 0.121941263 0.505 0.273 3.61E−68 Ranbp2 1.48E−72 0.208744477 0.596 0.338 3.67E−68 Mak16 1.48E−72 0.102725211 0.269 0.087 3.67E−68 Fbp1 1.92E−72 0.236214341 0.997 0.938 4.78E−68 Trip11 2.55E−72 0.163424021 0.429 0.2 6.32E−68 Ndufc2 2.97E−72 −0.202304309 0.639 0.579 7.36E−68 2900026A02Rik 4.76E−72 0.175166554 0.416 0.187 1.18E−67 Nr2f6 4.80E−72 −0.219631094 0.417 0.434 1.19E−67 Rc3h1 4.90E−72 0.165519544 0.33 0.122 1.22E−67 mt-Tq 5.18E−72 0.113221186 0.218 0.057 1.29E−67 Ash1l 6.20E−72 0.131678753 0.39 0.175 1.54E−67 Ywhag 6.59E−72 0.215838932 0.563 0.308 1.64E−67 Dpy19l1 7.13E−72 0.23352829 0.531 0.277 1.77E−67 Srpr 7.66E−72 0.223990237 0.647 0.387 1.90E−67 Cmah 7.80E−72 0.247781083 0.721 0.465 1.94E−67 Ssfa2 8.53E−72 0.162814615 0.354 0.141 2.12E−67 Apoc3 1.50E−71 0.187850611 0.999 0.993 3.73E−67 Atp5j 2.76E−71 −0.234964444 0.782 0.757 6.86E−67 Atp1a1 3.01E−71 0.261718912 0.709 0.457 7.48E−67 Abhd2 4.33E−71 0.14425027 0.302 0.105 1.07E−66 Ppp1r15a 5.70E−71 0.157408911 0.336 0.13 1.42E−66 Calr 6.41E−71 0.232562138 0.972 0.885 1.59E−66 Cyp2c55 9.78E−71 −0.316565473 0.103 0.243 2.43E−66 Skil 1.08E−70 0.126702219 0.269 0.086 2.67E−66 Fdx1 1.35E−70 −0.213846254 0.669 0.625 3.35E−66 Gls2 2.03E−70 0.296143664 0.868 0.657 5.05E−66 Alas1 2.26E−70 0.283195713 0.905 0.729 5.61E−66 Nup50 2.39E−70 0.121192082 0.374 0.164 5.94E−66 Cdip1 3.30E−70 0.161158186 0.514 0.273 8.19E−66 Pklr 3.64E−70 0.25984035 0.624 0.368 9.04E−66 Arf6 3.89E−70 0.132424754 0.407 0.189 9.65E−66 Acaca 4.34E−70 0.139911693 0.301 0.106 1.08E−65 Ftl1 4.45E−70 −0.346327339 0.394 0.409 1.10E−65 Tmem205 5.13E−70 −0.196745573 0.978 0.934 1.27E−65 Pnpla7 6.70E−70 0.251226201 0.807 0.572 1.66E−65 Hsd17b13 6.70E−70 0.351593878 0.907 0.74 1.66E−65 Ech1 1.07E−69 −0.191877671 0.908 0.856 2.66E−65 Osbpl1a 1.17E−69 0.247696779 0.721 0.473 2.89E−65 Baz1a 1.29E−69 0.111993205 0.249 0.077 3.21E−65 Arl8b 1.48E−69 0.198760529 0.468 0.228 3.68E−65 Tprkb 1.70E−69 −0.254084951 0.508 0.528 4.23E−65 Comt 2.11E−69 0.220396792 0.99 0.931 5.25E−65 Nucks1 2.41E−69 0.249253158 0.683 0.43 5.99E−65 Pim3 2.79E−69 0.280137371 0.764 0.537 6.92E−65 Nek7 4.21E−69 0.204786835 0.517 0.271 1.04E−64 Tm9sf2 5.17E−69 0.208759009 0.616 0.362 1.28E−64 P4hb 5.86E−69 0.204526132 0.995 0.941 1.46E−64 Ldha 7.13E−69 0.234882634 0.974 0.896 1.77E−64 Nolc1 7.21E−69 0.14652588 0.338 0.134 1.79E−64 Ripk1 8.04E−69 0.174862366 0.407 0.183 2.00E−64 Akr1c20 9.26E−69 −0.230255116 0.563 0.564 2.30E−64 Cldn1 9.68E−69 −0.246774022 0.21 0.306 2.40E−64 Mtus1 1.13E−68 0.268076242 0.674 0.42 2.80E−64 Ibtk 1.14E−68 0.188149661 0.485 0.247 2.82E−64 Kdm5c 1.27E−68 0.147833422 0.338 0.134 3.15E−64 Rdh7 1.46E−68 −0.197994968 0.993 0.969 3.62E−64 Me1 1.64E−68 0.229105587 0.699 0.447 4.06E−64 Ptplad1 1.76E−68 0.255273084 0.741 0.496 4.37E−64 Gm20528 1.77E−68 0.118200587 0.246 0.076 4.39E−64 Scarb2 6.53E−68 0.19345963 0.603 0.353 1.62E−63 Cnbp 8.69E−68 −0.203726646 0.828 0.778 2.16E−63 Hagh 1.07E−67 −0.157822564 0.933 0.858 2.65E−63 Prdx4 1.30E−67 −0.205807709 0.653 0.607 3.24E−63 Cep85 1.35E−67 0.171686021 0.383 0.167 3.35E−63 Cyp4a12a 1.81E−67 0.259776426 0.823 0.597 4.49E−63 Fas 1.94E−67 0.145849731 0.309 0.114 4.81E−63 Hdlbp 3.10E−67 0.267317937 0.894 0.713 7.69E−63 St3gal1 4.28E−67 0.192410856 0.454 0.221 1.06E−62 Gpc4 4.76E−67 0.16318479 0.349 0.141 1.18E−62 2310044G17Rik 5.00E−67 0.144057038 0.312 0.117 1.24E−62 Efhd2 8.01E−67 0.105846616 0.34 0.148 1.99E−62 Mctp2 1.20E−66 0.108025959 0.216 0.057 2.97E−62 Dhrs3 1.24E−66 −0.21828148 0.451 0.465 3.09E−62 Nedd4 1.43E−66 0.259978699 0.762 0.524 3.56E−62 Mafb 2.56E−66 0.216162055 0.577 0.33 6.37E−62 Aplp2 3.49E−66 0.234842456 0.844 0.625 8.67E−62 Rpl14 4.02E−66 −0.261157069 0.559 0.574 9.98E−62 Spred1 4.97E−66 0.110303756 0.234 0.069 1.23E−61 Cap1 6.06E−66 0.156999287 0.42 0.202 1.50E−61 Nploc4 6.75E−66 0.164369249 0.436 0.214 1.68E−61 Atl3 7.24E−66 0.191666389 0.506 0.27 1.80E−61 Wdr43 9.77E−66 0.116370658 0.343 0.146 2.43E−61 Kif21a 1.14E−65 0.240302185 0.537 0.293 2.82E−61 Macf1 1.72E−65 0.203727526 0.447 0.219 4.27E−61 Cmbl 1.79E−65 −0.198257983 0.724 0.678 4.46E−61 Alas2 2.13E−65 0.17568703 0.586 0.344 5.29E−61 Actr2 2.17E−65 0.170960453 0.638 0.394 5.39E−61 Gsk3b 2.37E−65 0.159364703 0.41 0.193 5.90E−61 Myo1b 2.40E−65 0.247482254 0.776 0.542 5.96E−61 Pcm1 2.44E−65 0.153416983 0.343 0.142 6.06E−61 Tesk2 2.49E−65 0.118095034 0.229 0.066 6.17E−61 Ddx21 2.61E−65 0.186649034 0.448 0.22 6.49E−61 Ahr 2.81E−65 0.139590211 0.349 0.151 6.97E−61 Itpr1 3.09E−65 0.161076343 0.356 0.152 7.68E−61 Uba1 3.33E−65 0.23027391 0.662 0.416 8.27E−61 Rap1b 3.43E−65 0.174034663 0.491 0.258 8.53E−61 Apoa2 3.55E−65 −0.174241915 1 1 8.81E−61 Lrrc28 3.89E−65 0.107467233 0.27 0.094 9.66E−61 Gdap2 5.12E−65 0.118267773 0.287 0.104 1.27E−60 Srsf4 5.16E−65 0.109628861 0.318 0.132 1.28E−60 Nop14 9.00E−65 0.120006548 0.288 0.108 2.24E−60 Copz1 9.86E−65 0.221023165 0.631 0.385 2.45E−60 Kmo 9.94E−65 0.262269388 0.891 0.732 2.47E−60 Slc2a2 1.09E−64 0.218249447 0.722 0.479 2.70E−60 Plbd2 1.24E−64 0.169456289 0.42 0.199 3.08E−60 Ahsa1 1.36E−64 0.126578677 0.458 0.24 3.38E−60 Ythdf3 1.76E−64 0.174850983 0.474 0.243 4.37E−60 Efna1 2.11E−64 0.256152989 0.551 0.309 5.25E−60 Lpin2 2.50E−64 0.232988713 0.817 0.597 6.20E−60 Ak3 2.62E−64 0.224559231 0.893 0.7 6.50E−60 Dnttip2 2.63E−64 0.166547988 0.418 0.199 6.54E−60 Supt6 2.69E−64 0.166662973 0.338 0.137 6.69E−60 Wasl 3.59E−64 0.178274463 0.449 0.223 8.92E−60 Agpat6 4.04E−64 0.242639639 0.749 0.517 1.00E−59 Gbe1 4.07E−64 0.183485273 0.577 0.338 1.01E−59 Lrrc8a 4.35E−64 0.100902509 0.255 0.085 1.08E−59 Il15ra 4.78E−64 0.129225351 0.314 0.125 1.19E−59 Cyp39a1 5.01E−64 0.136555896 0.295 0.11 1.24E−59 Cd1d1 5.24E−64 −0.182746213 0.644 0.612 1.30E−59 Nme1 5.76E−64 −0.195199734 0.674 0.622 1.43E−59 Snd1 6.86E−64 0.18406298 0.549 0.312 1.70E−59 Rbp1 7.01E−64 0.118452694 0.234 0.069 1.74E−59 Rcl1 1.12E−63 0.273905375 0.734 0.514 2.78E−59 Mknk2 1.34E−63 0.1323349 0.412 0.205 3.33E−59 Ndufb4 2.08E−63 −0.233018121 0.486 0.49 5.18E−59 Phf20l1 2.74E−63 0.123806334 0.422 0.212 6.81E−59 Map3k1 2.99E−63 0.100043219 0.184 0.044 7.43E−59 Gpam 3.62E−63 0.169852715 0.417 0.199 9.00E−59 Nipa2 4.23E−63 0.129532764 0.363 0.162 1.05E−58 Bsdc1 4.31E−63 0.137035108 0.381 0.178 1.07E−58 Riok2 4.51E−63 0.118813963 0.302 0.118 1.12E−58 Cebpz 4.87E−63 0.101120661 0.447 0.236 1.21E−58 Zfp36l1 8.15E−63 0.271823824 0.636 0.402 2.02E−58 Hif1a 1.10E−62 0.13634532 0.366 0.166 2.72E−58 Tnfrsf1b 1.17E−62 0.112815211 0.257 0.087 2.90E−58 Irf9 1.69E−62 0.102766206 0.329 0.145 4.18E−58 Ccnt1 1.79E−62 0.133253027 0.307 0.119 4.44E−58 Lmbrd2 1.97E−62 0.121703677 0.415 0.209 4.88E−58 Cryz 2.40E−62 0.137185877 0.468 0.251 5.96E−58 Fgd6 2.54E−62 0.16919996 0.348 0.147 6.30E−58 Larp4 2.70E−62 0.156912192 0.396 0.184 6.70E−58 Atp13a3 4.02E−62 0.197384706 0.65 0.41 9.98E−58 Fndc3b 5.18E−62 0.151940318 0.276 0.096 1.29E−57 Pum2 5.90E−62 0.14053782 0.382 0.177 1.47E−57 D4Wsu53e 6.52E−62 −0.201263472 0.393 0.385 1.62E−57 Slc27a2 1.00E−61 0.192264004 0.991 0.949 2.49E−57 Wdr26 1.03E−61 0.207089713 0.646 0.406 2.56E−57 Gns 1.32E−61 0.166751532 0.516 0.288 3.28E−57 Nrn1 1.50E−61 −0.19828092 0.704 0.675 3.72E−57 Pex11a 1.58E−61 0.185588983 0.681 0.441 3.93E−57 Enpep 2.39E−61 0.192022994 0.374 0.166 5.93E−57 Nr1i3 2.91E−61 −0.317940692 0.294 0.377 7.23E−57 Mup1 3.07E−61 −0.490972296 0.609 0.583 7.63E−57 Lrrc58 3.25E−61 0.196709613 0.597 0.359 8.07E−57 Dync1h1 3.32E−61 0.187521298 0.428 0.21 8.24E−57 Srrm2 3.41E−61 0.136584863 0.536 0.313 8.47E−57 Coa6 4.11E−61 −0.242879305 0.344 0.373 1.02E−56 Slc16a10 4.41E−61 0.194608601 0.547 0.315 1.09E−56 Crcp 4.75E−61 0.135362988 0.41 0.203 1.18E−56 Gclc 4.81E−61 −0.13277321 0.808 0.718 1.20E−56 Vkorc1 6.39E−61 −0.206999378 0.545 0.54 1.59E−56 Sfpq 7.82E−61 0.159417591 0.425 0.211 1.94E−56 Selk 8.43E−61 −0.155942939 0.545 0.486 2.09E−56 Dusp6 9.28E−61 0.205655249 0.491 0.261 2.30E−56 Minos1 1.00E−60 −0.201913176 0.638 0.595 2.49E−56 Mir692-1 1.02E−60 −0.20556011 0.012 0.126 2.54E−56 Ccrn4l 1.37E−60 0.108176603 0.243 0.08 3.41E−56 Slco1b2 1.44E−60 −0.207101647 0.976 0.951 3.57E−56 Scamp1 1.64E−60 0.122878314 0.398 0.197 4.08E−56 Scyl2 1.65E−60 0.130702939 0.344 0.151 4.09E−56 Farp1 1.94E−60 0.103692029 0.217 0.063 4.82E−56 Hist1h2bc 1.96E−60 −0.197841473 0.811 0.777 4.86E−56 Mib1 2.14E−60 0.148818716 0.438 0.226 5.31E−56 Ppp1r10 2.37E−60 0.113871639 0.292 0.115 5.89E−56 Sik3 2.40E−60 0.113008636 0.391 0.192 5.96E−56 Ptprj 2.49E−60 0.122121887 0.294 0.115 6.18E−56 Itch 2.57E−60 0.151077267 0.399 0.195 6.37E−56 Kif5b 3.75E−60 0.150172912 0.53 0.303 9.31E−56 Csde1 4.29E−60 0.209918785 0.797 0.577 1.07E−55 Ptprk 4.82E−60 0.158881882 0.354 0.156 1.20E−55 Ero1lb 5.45E−60 0.108914288 0.414 0.213 1.35E−55 Rab6a 6.68E−60 0.191200862 0.57 0.335 1.66E−55 Apex1 7.33E−60 0.137727736 0.396 0.191 1.82E−55 Cldn3 7.97E−60 −0.24877302 0.273 0.355 1.98E−55 Top1 9.07E−60 0.13764669 0.502 0.282 2.25E−55 Rab3gap1 9.76E−60 0.112449261 0.348 0.159 2.42E−55 Tspan4 1.12E−59 0.181956703 0.451 0.23 2.78E−55 Hao1 1.23E−59 0.196088416 0.924 0.758 3.06E−55 B4galt5 1.37E−59 0.112864448 0.229 0.07 3.41E−55 Cln8 1.39E−59 0.104477829 0.314 0.133 3.46E−55 Alkbh5 1.50E−59 0.198532353 0.507 0.279 3.73E−55 Birc6 1.50E−59 0.164860409 0.502 0.28 3.74E−55 4931406C07Rik 1.70E−59 −0.233221778 0.789 0.748 4.22E−55 Deb1 1.71E−59 −0.129415477 0.515 0.443 4.25E−55 Cyp3a59 2.07E−59 −0.263118105 0.281 0.344 5.15E−55 Mpc1 2.66E−59 −0.205050162 0.349 0.369 6.61E−55 Tnks2 3.54E−59 0.110931336 0.392 0.197 8.78E−55 Ip6k2 3.86E−59 0.142196587 0.392 0.192 9.57E−55 Derl2 5.00E−59 −0.12950658 0.573 0.499 1.24E−54 Zbtb41 6.03E−59 0.104784905 0.255 0.09 1.50E−54 Acacb 6.61E−59 0.172458783 0.33 0.137 1.64E−54 Ccdc25 6.64E−59 0.153512231 0.493 0.271 1.65E−54 Eif4g1 7.36E−59 0.201528669 0.865 0.669 1.83E−54 Mob1b 7.83E−59 0.134732265 0.407 0.203 1.94E−54 Rab1 8.62E−59 0.211939923 0.673 0.438 2.14E−54 Rad54l2 9.83E−59 0.101253342 0.251 0.092 2.44E−54 Cyp3a16 1.47E−58 −0.229013809 0.05 0.17 3.65E−54 Ghr 1.91E−58 0.197884255 0.963 0.833 4.74E−54 Vgll4 1.98E−58 0.152050279 0.363 0.164 4.92E−54 Rlim 2.11E−58 0.106781063 0.323 0.142 5.23E−54 Sdsl 2.12E−58 0.128070508 0.321 0.137 5.27E−54 Uqcrb 2.16E−58 −0.157541559 0.721 0.641 5.35E−54 Psmb1 2.75E−58 −0.18427868 0.822 0.759 6.83E−54 Ebpl 3.93E−58 −0.155251391 0.48 0.451 9.75E−54 Gnl2 4.20E−58 0.131907392 0.366 0.171 1.04E−53 F11 4.61E−58 0.183078168 0.512 0.287 1.15E−53 Map2k4 5.25E−58 0.119089109 0.36 0.17 1.30E−53 Sat1 5.31E−58 0.13070979 0.36 0.167 1.32E−53 Cpne3 5.59E−58 0.182285896 0.537 0.31 1.39E−53 C8g 6.46E−58 −0.1570956 0.965 0.91 1.61E−53 Arrdc4 7.07E−58 0.100382723 0.207 0.061 1.76E−53 Cltc 7.52E−58 0.238358233 0.647 0.414 1.87E−53 Ptpn11 7.96E−58 0.122589174 0.418 0.218 1.98E−53 Dio1 8.16E−58 −0.238782365 0.544 0.542 2.03E−53 Akr1c19 8.22E−58 −0.179403044 0.547 0.527 2.04E−53 Cct8 9.67E−58 0.156517607 0.674 0.445 2.40E−53 Dpyd 1.41E−57 0.207189814 0.857 0.659 3.51E−53 4833439L19Rik 1.42E−57 0.107135389 0.341 0.158 3.53E−53 Mrps18c 1.45E−57 −0.211258064 0.403 0.394 3.61E−53 Mpzl2 1.66E−57 0.112096706 0.33 0.148 4.12E−53 Masp1 1.68E−57 0.120716874 0.347 0.16 4.16E−53 Tram1 1.72E−57 0.180903738 0.737 0.512 4.26E−53 Uggt1 2.14E−57 0.147681553 0.408 0.204 5.32E−53 Sec31a 2.29E−57 0.151339369 0.53 0.31 5.68E−53 Reep3 2.41E−57 0.201856133 0.654 0.422 5.99E−53 Baz1b 2.42E−57 0.121966091 0.416 0.215 6.02E−53 Csnk2b 2.44E−57 0.1035331 0.39 0.196 6.06E−53 Hsdl2 2.60E−57 0.206098727 0.669 0.438 6.46E−53 Eif4b 3.03E−57 0.163112238 0.666 0.438 7.53E−53 Tmem19 3.40E−57 0.214785487 0.693 0.465 8.45E−53 Dpp9 3.50E−57 0.141994305 0.378 0.182 8.68E−53 Erap1 3.86E−57 0.136126562 0.452 0.244 9.59E−53 Sf3b1 3.86E−57 0.196390125 0.637 0.406 9.60E−53 Gas5 3.98E−57 −0.204205779 0.552 0.527 9.89E−53 Gys2 4.07E−57 0.152105722 0.582 0.358 1.01E−52 Atp8b1 4.27E−57 0.12732077 0.372 0.182 1.06E−52 Impad1 4.33E−57 0.115657521 0.464 0.263 1.08E−52 BCl2l13 4.37E−57 0.100287331 0.328 0.152 1.08E−52 Rps15 5.66E−57 −0.213338023 0.581 0.528 1.41E−52 Mapk14 5.96E−57 0.137832043 0.44 0.232 1.48E−52 Ogdh 6.23E−57 0.220189108 0.601 0.37 1.55E−52 Huwe1 7.13E−57 0.177152033 0.536 0.314 1.77E−52 Slc25a1 8.37E−57 0.187178873 0.724 0.499 2.08E−52 Dennd1b 8.64E−57 0.104019094 0.285 0.117 2.14E−52 Naa50 9.38E−57 0.187968549 0.586 0.358 2.33E−52 Nab1 1.35E−56 0.151021868 0.533 0.315 3.36E−52 Spag7 1.45E−56 0.101789122 0.331 0.151 3.60E−52 F11r 1.56E−56 0.135500375 0.421 0.216 3.88E−52 Pah 1.79E−56 0.196282042 0.983 0.891 4.44E−52 Uhrf1bp1l 2.27E−56 0.100980999 0.397 0.207 5.63E−52 Slc30a9 2.34E−56 0.116028379 0.438 0.235 5.80E−52 Psap 2.57E−56 0.145158043 0.736 0.513 6.38E−52 Nr0b2 2.67E−56 −0.203060823 0.227 0.28 6.63E−52 Ggcx 2.98E−56 0.118127678 0.421 0.225 7.41E−52 Itih1 3.10E−56 0.213777239 0.946 0.816 7.71E−52 Pdzd8 3.45E−56 0.138689794 0.407 0.206 8.57E−52 Ppp2r2d 3.50E−56 0.110486018 0.45 0.247 8.70E−52 Vwa8 3.52E−56 0.184402682 0.534 0.311 8.74E−52 Mcl1 3.90E−56 0.206406082 0.601 0.371 9.67E−52 Acadl 4.72E−56 0.192143091 0.819 0.612 1.17E−51 Cebpg 4.86E−56 0.13869941 0.447 0.239 1.21E−51 Trp53inp2 4.90E−56 0.176936721 0.655 0.428 1.22E−51 Kpna1 5.49E−56 0.161541953 0.411 0.206 1.36E−51 Ndufa4 6.92E−56 −0.196233158 0.941 0.889 1.72E−51 Chchd1 6.96E−56 −0.178218308 0.469 0.438 1.73E−51 Rhou 6.96E−56 0.192074068 0.559 0.333 1.73E−51 Pcca 7.64E−56 0.150589178 0.594 0.373 1.90E−51 Ap3m1 9.11E−56 0.133817705 0.408 0.211 2.26E−51 Arl5a 9.40E−56 0.169926786 0.508 0.289 2.33E−51 Clcn4-2 1.11E−55 0.160606741 0.492 0.276 2.75E−51 Ugt3a1 1.20E−55 0.100417636 0.243 0.088 2.97E−51 Pank1 1.25E−55 0.222539616 0.873 0.704 3.11E−51 Zfp110 1.53E−55 0.112121418 0.306 0.131 3.80E−51 Eif4e2 2.21E−55 0.11430292 0.472 0.268 5.48E−51 Rn7sk 2.30E−55 −0.149783999 0.242 0.186 5.70E−51 Nufip2 2.32E−55 0.118078669 0.318 0.14 5.76E−51 Phlda1 2.67E−55 0.201287476 0.583 0.356 6.64E−51 Srsf6 2.84E−55 0.127543054 0.467 0.261 7.06E−51 Ugt1a1 2.92E−55 0.183517826 0.502 0.283 7.25E−51 Amfr 2.93E−55 0.184512887 0.738 0.516 7.27E−51 Nars 2.97E−55 0.191856779 0.696 0.471 7.38E−51 Paip1 3.87E−55 0.108346951 0.471 0.272 9.62E−51 Hspa4 4.00E−55 0.171672026 0.728 0.506 9.94E−51 Arf4 5.70E−55 0.159979368 0.58 0.36 1.42E−50 Ubxn7 6.79E−55 0.100852418 0.267 0.107 1.69E−50 Uap1 7.92E−55 0.104727103 0.298 0.126 1.97E−50 Idh1 8.76E−55 0.208112098 0.921 0.766 2.18E−50 Lysmd3 9.24E−55 0.119777827 0.352 0.166 2.29E−50 Arih1 9.58E−55 0.113132381 0.408 0.216 2.38E−50 Furin 9.60E−55 0.191384876 0.643 0.417 2.38E−50 Fam214a 9.86E−55 0.133009262 0.448 0.248 2.45E−50 0610005C13Rik 1.05E−54 −0.2011928 0.677 0.653 2.60E−50 Atp5a1 1.05E−54 0.174138529 0.984 0.895 2.60E−50 Med13 1.07E−54 0.128372588 0.353 0.168 2.66E−50 Ddx17 1.15E−54 0.159893824 0.491 0.277 2.85E−50 Vps13d 1.17E−54 0.117630793 0.367 0.181 2.91E−50 Tmem30a 1.18E−54 0.147452363 0.858 0.664 2.94E−50 Glyr1 1.26E−54 0.139056743 0.476 0.269 3.14E−50 Pank3 1.32E−54 0.128601194 0.451 0.251 3.28E−50 Ranbp9 1.35E−54 0.114807175 0.35 0.169 3.36E−50 St3gal4 1.41E−54 0.159434184 0.456 0.244 3.49E−50 Etf1 1.44E−54 0.198764917 0.636 0.409 3.59E−50 Tbc1d15 1.56E−54 0.1185677 0.443 0.244 3.88E−50 Ndufb8 1.63E−54 −0.158878768 0.79 0.746 4.05E−50 Ttyh2 1.67E−54 0.113959235 0.362 0.179 4.14E−50 8430408G22Rik 1.98E−54 −0.221336883 0.336 0.392 4.93E−50 Fam168b 3.06E−54 0.106478831 0.292 0.124 7.59E−50 Gdf15 3.33E−54 0.246982665 0.595 0.37 8.27E−50 Gpd1 4.47E−54 0.200332863 0.856 0.665 1.11E−49 Cgnl1 4.57E−54 0.139773771 0.44 0.238 1.13E−49 Ndufs4 4.82E−54 −0.100492283 0.662 0.562 1.20E−49 Brd2 4.94E−54 0.258446853 0.629 0.408 1.23E−49 Lclat1 4.98E−54 0.119397464 0.344 0.162 1.24E−49 Dnajc5 5.50E−54 0.134563348 0.42 0.223 1.37E−49 Tlcd2 5.97E−54 −0.168255558 0.563 0.536 1.48E−49 Mon2 6.36E−54 0.112969342 0.393 0.206 1.58E−49 Calu 7.05E−54 0.135275013 0.438 0.236 1.75E−49 Mup14 7.18E−54 −0.340890047 0.699 0.616 1.78E−49 Onecut2 9.06E−54 0.133054586 0.53 0.323 2.25E−49 Swi5 9.79E−54 −0.115995539 0.572 0.501 2.43E−49 Hopx 1.01E−53 0.11914525 0.407 0.212 2.50E−49 Gtf2b 1.35E−53 0.140783181 0.383 0.189 3.35E−49 Cebpb 1.82E−53 −0.114648972 0.548 0.45 4.53E−49 Ubr5 1.96E−53 0.130354935 0.447 0.248 4.86E−49 Prkd3 2.04E−53 −0.146969299 0.538 0.49 5.07E−49 Akap13 2.11E−53 0.147641979 0.416 0.218 5.25E−49 Xpr1 2.30E−53 0.117363241 0.294 0.125 5.70E−49 Adam9 2.79E−53 0.145575974 0.406 0.206 6.92E−49 Hc 3.23E−53 0.223732951 0.976 0.903 8.02E−49 Atp5j2 3.89E−53 −0.218750887 0.887 0.852 9.67E−49 Ifitm2 3.99E−53 0.199025687 0.568 0.347 9.91E−49 Bpnt1 4.01E−53 0.113495161 0.461 0.264 9.96E−49 Cp 6.52E−53 0.17916098 0.993 0.943 1.62E−48 Rabgap1l 6.94E−53 0.13415085 0.338 0.158 1.72E−48 Adh6-ps1 8.20E−53 −0.22400228 0.259 0.313 2.04E−48 Aars 8.79E−53 0.199299553 0.699 0.479 2.18E−48 Slc30a10 8.80E−53 0.166623301 0.442 0.238 2.19E−48 Eps15 1.07E−52 0.104532417 0.351 0.173 2.65E−48 Nckap1 1.10E−52 0.109949167 0.552 0.349 2.72E−48 Dap 1.10E−52 0.20987441 0.842 0.654 2.72E−48 Slc16a1 1.15E−52 0.136030092 0.383 0.191 2.85E−48 Ubb 1.22E−52 −0.263773933 0.448 0.45 3.04E−48 Zfand4 1.71E−52 0.121779444 0.309 0.136 4.25E−48 Ireb2 1.72E−52 0.163596475 0.536 0.321 4.27E−48 Ugdh 1.95E−52 0.175644914 0.808 0.604 4.84E−48 Gm24245 1.97E−52 −0.254157233 0.192 0.214 4.90E−48 Ces1g 1.99E−52 −0.129319624 0.627 0.569 4.93E−48 Ywhab 2.03E−52 0.186791118 0.656 0.434 5.04E−48 Hgfac 2.16E−52 0.181878452 0.66 0.438 5.38E−48 Rangap1 2.23E−52 0.116918523 0.44 0.244 5.53E−48 Purb 2.27E−52 0.118154372 0.337 0.158 5.63E−48 Cpeb4 2.49E−52 0.107417249 0.496 0.299 6.19E−48 Dusp3 2.73E−52 0.121478974 0.415 0.221 6.78E−48 Golph3 2.78E−52 0.111893985 0.415 0.223 6.90E−48 Rpl35 2.79E−52 −0.175144379 0.216 0.225 6.93E−48 Prdx1 3.09E−52 −0.174743472 0.971 0.927 7.67E−48 Capzb 3.11E−52 0.162969545 0.561 0.344 7.71E−48 Parva 3.29E−52 0.146537234 0.504 0.296 8.18E−48 Nr5a2 3.59E−52 0.139283512 0.425 0.228 8.91E−48 Pdcd6ip 3.70E−52 0.181372134 0.556 0.338 9.18E−48 Akr1c14 3.92E−52 −0.173913844 0.758 0.707 9.73E−48 Sppl2a 4.25E−52 0.169493485 0.769 0.56 1.06E−47 Gstm1 4.43E−52 −0.221666006 0.984 0.935 1.10E−47 As3mt 5.14E−52 0.123667446 0.359 0.175 1.28E−47 Atp5d 5.35E−52 0.209976794 0.871 0.712 1.33E−47 Ahcyl2 5.51E−52 0.103953438 0.231 0.084 1.37E−47 Man1a 5.66E−52 0.190591338 0.799 0.595 1.40E−47 Atp11b 5.99E−52 0.129558793 0.388 0.199 1.49E−47 Arcn1 6.54E−52 0.158407448 0.582 0.366 1.62E−47 Med1 6.78E−52 0.100895572 0.274 0.116 1.68E−47 Narf 6.98E−52 0.163638744 0.46 0.253 1.73E−47 Chordc1 9.30E−52 0.116647052 0.391 0.204 2.31E−47 Klkb1 1.08E−51 −0.123984363 0.409 0.363 2.67E−47 Ssr3 1.10E−51 0.214262703 0.796 0.596 2.74E−47 Ubr4 1.11E−51 0.17740179 0.455 0.25 2.77E−47 Tmf1 1.20E−51 0.127343798 0.512 0.307 2.98E−47 Lin7c 1.26E−51 0.133833672 0.384 0.194 3.12E−47 Ifrd1 1.28E−51 0.175156039 0.379 0.185 3.17E−47 Ppp6r3 1.29E−51 0.122373925 0.378 0.191 3.20E−47 Sdc1 1.42E−51 0.202649914 0.686 0.469 3.52E−47 Cd164 1.47E−51 0.139864927 0.749 0.542 3.66E−47 Zfr 1.55E−51 0.136139327 0.486 0.283 3.85E−47 Sec23a 1.59E−51 0.106870804 0.487 0.291 3.94E−47 Rraga 1.62E−51 0.117337603 0.383 0.196 4.03E−47 Pxmp4 1.77E−51 0.233212684 0.731 0.526 4.40E−47 Nlrp12 1.80E−51 0.153172692 0.648 0.43 4.46E−47 Ythdf1 1.80E−51 0.102530375 0.317 0.147 4.48E−47 Fam195a 1.82E−51 −0.190271304 0.355 0.373 4.52E−47 Mier1 1.86E−51 0.10569398 0.409 0.224 4.61E−47 Mrp63 2.10E−51 −0.184375029 0.563 0.531 5.21E−47 Bhmt2 2.27E−51 −0.108586116 0.719 0.637 5.63E−47 Usp33 2.40E−51 0.102734502 0.35 0.176 5.95E−47 1110008F13Rik 2.78E−51 −0.197564988 0.666 0.648 6.90E−47 Plaa 3.40E−51 0.113721305 0.383 0.198 8.45E−47 6-Mar 3.70E−51 0.140127792 0.56 0.352 9.18E−47 Uqcr11 4.09E−51 −0.196760374 0.918 0.879 1.01E−46 Celf1 4.96E−51 0.126385885 0.515 0.313 1.23E−46 Lmbrd1 5.80E−51 0.113233603 0.474 0.279 1.44E−46 Cat 6.02E−51 0.151152692 0.998 0.971 1.50E−46 Gm4952 6.05E−51 −0.180740052 0.551 0.533 1.50E−46 Iars 6.26E−51 0.114030301 0.329 0.155 1.56E−46 Gna12 6.93E−51 −0.191090072 0.352 0.354 1.72E−46 Sh3d19 7.12E−51 0.107931616 0.467 0.275 1.77E−46 Hadhb 7.55E−51 −0.134029493 0.383 0.33 1.88E−46 Mfn1 8.21E−51 0.11641477 0.353 0.175 2.04E−46 Ppm1k 8.28E−51 −0.198117939 0.469 0.45 2.06E−46 Pmpca 8.29E−51 0.132846702 0.45 0.254 2.06E−46 Hint1 8.36E−51 −0.15108001 0.915 0.858 2.08E−46 Api5 8.58E−51 0.12264057 0.358 0.176 2.13E−46 Zzef1 9.17E−51 0.111336837 0.282 0.122 2.28E−46 Cltb 9.26E−51 0.111216553 0.533 0.333 2.30E−46 Ssr1 1.00E−50 0.140942479 0.546 0.339 2.48E−46 Vcpip1 1.17E−50 0.134850634 0.437 0.241 2.90E−46 Slc35d1 1.46E−50 0.1666456 0.651 0.435 3.63E−46 Sult1d1 1.70E−50 −0.183796178 0.739 0.684 4.21E−46 Bzw1 1.98E−50 0.162308789 0.558 0.344 4.93E−46 Lats1 2.50E−50 0.101875138 0.317 0.149 6.22E−46 Ces1e 2.57E−50 0.166391723 0.779 0.576 6.37E−46 Blvrb 3.17E−50 −0.243251643 0.562 0.564 7.88E−46 Abca6 3.37E−50 0.198869605 0.719 0.507 8.37E−46 Als2 3.42E−50 0.131619164 0.32 0.147 8.48E−46 Rps18 3.43E−50 −0.269206741 0.584 0.578 8.51E−46 Cflar 3.48E−50 0.110786697 0.421 0.231 8.63E−46 Gss 3.67E−50 0.141566962 0.557 0.346 9.10E−46 Nudt4 3.71E−50 0.183172596 0.773 0.568 9.22E−46 Dnm1l 3.84E−50 0.110229955 0.414 0.227 9.53E−46 Fabp2 3.96E−50 −0.226921259 0.631 0.622 9.82E−46 Pkp4 4.09E−50 0.102644807 0.445 0.258 1.02E−45 Grlf1 4.50E−50 0.163008664 0.457 0.257 1.12E−45 Wdr82 4.69E−50 0.105623725 0.313 0.144 1.17E−45 Apol7a 5.09E−50 −0.165242629 0.39 0.382 1.26E−45 Son 5.49E−50 0.188921988 0.573 0.358 1.36E−45 Lgals9 5.83E−50 0.184003378 0.936 0.793 1.45E−45 Sec24d 6.42E−50 0.138799708 0.447 0.251 1.60E−45 Insr 6.47E−50 0.133005386 0.495 0.295 1.61E−45 Sel1l 6.89E−50 0.100522207 0.586 0.392 1.71E−45 Rtfdc1 7.59E−50 0.16242752 0.627 0.412 1.88E−45 Hnrnpab 8.17E−50 0.135931142 0.768 0.565 2.03E−45 Itpr2 8.28E−50 0.100488718 0.353 0.179 2.06E−45 Serbp1 1.03E−49 0.186271124 0.824 0.634 2.55E−45 Dnaja3 1.31E−49 0.137126337 0.63 0.42 3.25E−45 Tmem50a 1.46E−49 0.122161634 0.533 0.33 3.62E−45 Bnip2 1.64E−49 0.101515343 0.371 0.196 4.07E−45 Osbpl9 1.68E−49 0.161985999 0.661 0.448 4.17E−45 Uhmk1 1.72E−49 0.128955106 0.354 0.177 4.26E−45 Hsd17b2 1.78E−49 −0.143475762 0.775 0.711 4.42E−45 Ttc36 1.82E−49 −0.175280872 0.983 0.95 4.52E−45 Pqlc1 1.93E−49 −0.161639859 0.364 0.36 4.79E−45 Setd2 2.06E−49 0.108533511 0.333 0.165 5.12E−45 Ppp3r1 2.23E−49 0.111279553 0.309 0.142 5.55E−45 Nek6 2.72E−49 0.136185787 0.436 0.242 6.76E−45 Ugt2a3 2.99E−49 −0.147859157 0.84 0.773 7.43E−45 Zbtb20 3.04E−49 0.197963292 0.657 0.445 7.55E−45 Eprs 3.05E−49 0.19400896 0.7 0.488 7.57E−45 A1cf 3.13E−49 0.163393145 0.66 0.449 7.78E−45 Rab18 4.02E−49 0.139929705 0.603 0.393 9.99E−45 Dnajc11 4.18E−49 0.117471006 0.346 0.17 1.04E−44 Ethe1 5.13E−49 −0.13151581 0.532 0.49 1.27E−44 Agt 5.58E−49 0.169771558 0.941 0.817 1.39E−44 S100a1 6.36E−49 −0.11753536 0.75 0.661 1.58E−44 Lrrc59 6.94E−49 0.163232541 0.484 0.28 1.72E−44 Ubr2 6.97E−49 0.158348096 0.464 0.265 1.73E−44 Ppp2r5e 7.06E−49 0.107846882 0.445 0.259 1.75E−44 Slain2 7.34E−49 0.115222374 0.354 0.179 1.82E−44 Psma1 7.88E−49 −0.105583275 0.606 0.521 1.96E−44 Aco2 9.05E−49 0.155048742 0.702 0.493 2.25E−44 Faah 1.00E−48 0.139243096 0.623 0.415 2.48E−44 Pten 1.24E−48 0.166403783 0.669 0.458 3.07E−44 Akr1c13 1.24E−48 −0.11922584 0.517 0.457 3.09E−44 Cbs 1.27E−48 0.199528185 0.901 0.749 3.15E−44 Slc25a5 1.29E−48 −0.141114149 0.778 0.717 3.19E−44 2610507B11Rik 1.29E−48 0.14984373 0.513 0.31 3.21E−44 Slc38a10 1.30E−48 0.110122581 0.481 0.291 3.22E−44 Ttc23 1.33E−48 0.111807305 0.375 0.199 3.30E−44 Pdhb 1.57E−48 0.129818342 0.67 0.468 3.89E−44 Psma2 1.59E−48 −0.123180488 0.607 0.538 3.95E−44 Ociad1 1.69E−48 0.138322793 0.659 0.45 4.19E−44 Dhcr24 1.81E−48 0.165813919 0.932 0.783 4.50E−44 Car8 2.09E−48 −0.101794556 0.539 0.465 5.19E−44 Trim25 2.14E−48 0.126667357 0.421 0.233 5.31E−44 Pygl 2.32E−48 0.19507544 0.92 0.776 5.77E−44 Prkar1a 2.53E−48 0.165756705 0.67 0.46 6.28E−44 Cxadr 2.55E−48 0.144004472 0.545 0.345 6.32E−44 Commd6 4.18E−48 −0.168923514 0.391 0.39 1.04E−43 Chchd2 4.90E−48 −0.200916511 0.953 0.916 1.22E−43 Cacul1 5.03E−48 0.127222559 0.423 0.236 1.25E−43 Cyp2f2 5.05E−48 0.275177176 0.965 0.863 1.25E−43 Nfe2l1 5.22E−48 0.132452495 0.497 0.303 1.30E−43 Dennd5b 5.95E−48 0.129106401 0.531 0.334 1.48E−43 Klc4 6.82E−48 0.102388831 0.4 0.223 1.69E−43 Glol 6.86E−48 −0.154642914 0.804 0.749 1.70E−43 Cul4a 7.75E−48 0.117942041 0.494 0.303 1.93E−43 Cul1 7.81E−48 0.116195619 0.511 0.313 1.94E−43 Atxn7l3b 7.88E−48 0.191387966 0.686 0.476 1.96E−43 Dnajc19 8.94E−48 −0.156899631 0.412 0.387 2.22E−43 Col18a1 9.46E−48 0.159648412 0.934 0.79 2.35E−43 Tmem243 1.05E−47 −0.137755038 0.613 0.557 2.61E−43 Nudt12 1.13E−47 0.112919569 0.446 0.26 2.80E−43 Metap2 1.14E−47 0.120185231 0.479 0.285 2.83E−43 Rpl36al 1.22E−47 −0.186625637 0.601 0.551 3.02E−43 1300002K09Rik 1.26E−47 0.134310334 0.713 0.514 3.12E−43 F5 1.41E−47 0.202197412 0.886 0.728 3.50E−43 Creld2 1.42E−47 0.138271923 0.494 0.296 3.53E−43 Agpat2 1.57E−47 −0.124813217 0.699 0.638 3.90E−43 Tmem248 1.61E−47 0.118092361 0.428 0.242 3.99E−43 Ppp2ca 1.61E−47 0.154757155 0.64 0.43 4.00E−43 Paics 1.65E−47 0.198478345 0.842 0.662 4.10E−43 Gspt1 1.72E−47 0.141363417 0.665 0.458 4.27E−43 Prdx3 1.89E−47 0.134710601 0.504 0.305 4.69E−43 Dnaja2 1.92E−47 0.160071794 0.612 0.402 4.77E−43 Psma6 1.96E−47 −0.114376366 0.765 0.675 4.87E−43 Slco1a1 2.00E−47 0.134873793 0.927 0.777 4.97E−43 Psma4 2.34E−47 −0.153086391 0.544 0.495 5.82E−43 Cyp2e1 2.61E−47 −0.301497571 0.817 0.911 6.49E−43 Gsta2 2.63E−47 −0.188661153 0.296 0.333 6.53E−43 Nrd1 3.09E−47 0.127908934 0.495 0.298 7.68E−43 C1d 3.10E−47 −0.142249747 0.377 0.354 7.70E−43 Vps37a 3.47E−47 0.104057579 0.464 0.278 8.62E−43 Nadk 3.81E−47 0.15446959 0.661 0.454 9.47E−43 Bckdha 4.33E−47 −0.144632079 0.693 0.63 1.08E−42 2-Sep 4.81E−47 0.114840052 0.409 0.227 1.20E−42 Mtpn 5.14E−47 0.145939415 0.657 0.452 1.28E−42 Fxr1 5.32E−47 0.101455713 0.421 0.241 1.32E−42 Rabac1 5.83E−47 −0.211715679 0.522 0.524 1.45E−42 Osbpl8 7.65E−47 0.102268292 0.354 0.185 1.90E−42 Slc31a1 8.37E−47 0.182041621 0.693 0.486 2.08E−42 Pde4dip 9.36E−47 0.135519348 0.442 0.251 2.32E−42 Lamtor4 9.51E−47 −0.133507304 0.42 0.372 2.36E−42 Abce1 9.90E−47 0.132820596 0.506 0.31 2.46E−42 Sco2 1.08E−46 −0.198692618 0.507 0.508 2.68E−42 Erp44 1.22E−46 0.108210732 0.525 0.336 3.03E−42 Lman1 1.25E−46 0.147126353 0.838 0.655 3.12E−42 Tm4sf4 1.42E−46 0.105750727 0.439 0.256 3.53E−42 Hook1 1.44E−46 0.118548066 0.481 0.291 3.58E−42 Osbp 1.72E−46 0.106784104 0.323 0.158 4.27E−42 Ninj1 1.74E−46 −0.146496556 0.647 0.6 4.33E−42 Yme1l1 1.75E−46 0.128865754 0.657 0.455 4.35E−42 Gnas 1.82E−46 0.159624116 0.947 0.82 4.52E−42 Nampt 1.96E−46 0.120285537 0.434 0.248 4.87E−42 Pdha1 2.13E−46 0.133742662 0.675 0.474 5.28E−42 AI182371 2.26E−46 0.179018804 0.81 0.622 5.62E−42 Crem 2.31E−46 0.101912709 0.392 0.218 5.74E−42 Mrpl41 2.54E−46 −0.172436199 0.341 0.348 6.30E−42 Timm13 2.82E−46 −0.204422177 0.695 0.671 7.01E−42 Fyttd1 3.01E−46 0.101452644 0.354 0.186 7.47E−42 Becn1 3.03E−46 0.126325957 0.382 0.204 7.51E−42 Khk 3.09E−46 0.101177619 0.976 0.863 7.67E−42 Gnai3 3.18E−46 0.126569862 0.559 0.363 7.91E−42 Gchfr 3.33E−46 −0.152643272 0.833 0.768 8.26E−42 Mapk1 3.43E−46 0.120232033 0.453 0.27 8.53E−42 Gyk 3.49E−46 0.150378816 0.553 0.35 8.66E−42 Ywhae 3.56E−46 0.148553311 0.758 0.56 8.85E−42 Ppp1r15b 4.10E−46 0.120958229 0.48 0.291 1.02E−41 Ctnna1 4.17E−46 0.12068953 0.588 0.391 1.04E−41 Gckr 4.43E−46 0.141702795 0.505 0.307 1.10E−41 Sbfm1 4.65E−46 −0.132167436 0.544 0.484 1.15E−41 Etnk1 4.96E−46 0.15045907 0.527 0.328 1.23E−41 Trap1 6.48E−46 0.101198423 0.731 0.541 1.61E−41 Ndufs6 6.75E−46 −0.195648216 0.771 0.724 1.68E−41 Crot 7.15E−46 −0.119666122 0.988 0.942 1.77E−41 Mbnl1 7.21E−46 0.103083775 0.48 0.297 1.79E−41 Aldoa 7.94E−46 0.122026615 0.511 0.316 1.97E−41 Copb1 8.11E−46 0.132958439 0.628 0.429 2.01E−41 AW112010 8.57E−46 −0.128497272 0.473 0.435 2.13E−41 Sptbn1 8.60E−46 0.11420622 0.445 0.26 2.14E−41 Cxcl12 1.11E−45 −0.119856412 0.483 0.419 2.77E−41 Zfp106 1.17E−45 0.116608539 0.437 0.254 2.91E−41 9430023L20Rik 1.20E−45 −0.164422856 0.264 0.282 2.99E−41 C1rl 1.24E−45 0.10472398 0.601 0.404 3.09E−41 Secisbp2l 1.36E−45 0.117268869 0.506 0.317 3.37E−41 5-Mar 1.37E−45 0.113105187 0.508 0.317 3.40E−41 Golga4 1.44E−45 0.120034328 0.5 0.31 3.56E−41 Ccdc50 1.54E−45 0.117452166 0.428 0.246 3.83E−41 Map1lc3b 1.57E−45 0.167697241 0.602 0.395 3.90E−41 Pigyl 1.75E−45 −0.14064376 0.312 0.3 4.34E−41 Cd81 1.93E−45 −0.10012454 0.764 0.675 4.80E−41 Clmn 2.12E−45 0.159639031 0.509 0.31 5.25E−41 Tsc22d1 2.25E−45 −0.235196773 0.158 0.242 5.58E−41 Ap1g1 2.57E−45 0.111599757 0.431 0.252 6.39E−41 Usp32 2.65E−45 0.103466162 0.28 0.127 6.57E−41 Bola1 2.65E−45 −0.12138055 0.347 0.307 6.59E−41 Xiap 2.90E−45 0.11609823 0.575 0.378 7.20E−41 Edem1 2.95E−45 0.172255296 0.635 0.429 7.33E−41 Stat1 3.53E−45 0.130244409 0.353 0.18 8.76E−41 Hdac11 3.81E−45 −0.196507741 0.251 0.285 9.47E−41 Fah 3.98E−45 0.188483379 0.941 0.834 9.89E−41 Acad11 4.08E−45 0.148432334 0.759 0.564 1.01E−40 Uso1 4.50E−45 0.125106881 0.634 0.434 1.12E−40 Tacc1 5.30E−45 0.10371879 0.339 0.171 1.32E−40 St6gal1 5.67E−45 0.12698386 0.405 0.226 1.41E−40 Tkt 5.71E−45 0.104051911 0.615 0.424 1.42E−40 Sar1a 5.99E−45 0.138437968 0.541 0.343 1.49E−40 Adh4 6.51E−45 −0.13090615 0.571 0.521 1.62E−40 Pbld1 6.67E−45 −0.1818338 0.592 0.565 1.66E−40 Crp 6.74E−45 0.178468102 0.905 0.756 1.67E−40 Spcs1 7.39E−45 −0.141150139 0.446 0.413 1.84E−40 Tgoln1 7.77E−45 0.176355766 0.768 0.575 1.93E−40 Erf3b 7.78E−45 0.128303984 0.563 0.366 1.93E−40 Gstt3 7.97E−45 −0.159722425 0.296 0.286 1.98E−40 Gstm4 8.06E−45 −0.157553603 0.478 0.444 2.00E−40 Neat1 9.67E−45 0.164921803 0.293 0.135 2.40E−40 Rps19 1.08E−44 −0.151004347 0.562 0.474 2.69E−40 Ndufb2 1.15E−44 −0.154329774 0.685 0.629 2.86E−40 Ndufa2 1.15E−44 −0.194549142 0.792 0.738 2.86E−40 Cyp4f15 1.21E−44 −0.136129684 0.486 0.428 3.00E−40 Anp32a 1.28E−44 −0.154984115 0.436 0.413 3.17E−40 Rps15a 1.29E−44 −0.139214885 0.337 0.296 3.21E−40 Tmed7 1.30E−44 0.118885811 0.557 0.367 3.22E−40 Gfm1 1.32E−44 0.132118047 0.525 0.332 3.28E−40 Psme2 1.47E−44 −0.120525793 0.315 0.276 3.64E−40 Cyp3a44 1.56E−44 −0.205800676 0.164 0.183 3.87E−40 Nfia 1.59E−44 0.132814201 0.43 0.245 3.95E−40 Prrc2c 1.86E−44 0.108378548 0.369 0.201 4.62E−40 Surf4 1.87E−44 0.150111361 0.746 0.551 4.64E−40 1110058L19Rik 2.30E−44 −0.160260673 0.272 0.281 5.71E−40 Hspa9 2.77E−44 0.158702904 0.947 0.824 6.88E−40 Vamp8 2.81E−44 −0.111795351 0.713 0.636 6.98E−40 Sdha 2.85E−44 0.152056738 0.902 0.747 7.08E−40 Proz 2.91E−44 0.135145053 0.724 0.53 7.22E−40 Brk1 2.94E−44 −0.119149676 0.393 0.349 7.31E−40 Mrps21 2.99E−44 −0.121789459 0.257 0.215 7.43E−40 Rnase4 3.02E−44 0.221993349 0.986 0.921 7.49E−40 Ccs 3.19E−44 −0.107043033 0.754 0.676 7.91E−40 Trip12 3.24E−44 0.158568104 0.544 0.345 8.06E−40 Acadsb 3.49E−44 0.161705277 0.79 0.601 8.66E−40 Dlg1 3.65E−44 0.120208184 0.38 0.208 9.05E−40 Rpl34 3.76E−44 −0.130799019 0.465 0.398 9.34E−40 Nr1h4 5.00E−44 0.142664592 0.634 0.434 1.24E−39 Qprt 5.29E−44 0.156064415 0.698 0.498 1.31E−39 Spop 7.17E−44 0.114116164 0.59 0.394 1.78E−39 Fdft1 7.30E−44 −0.11322184 0.369 0.335 1.81E−39 Chd4 7.40E−44 −0.114509098 0.484 0.39 1.84E−39 Afm 7.47E−44 0.159606308 0.745 0.55 1.86E−39 Dhx15 9.21E−44 0.107938501 0.456 0.276 2.29E−39 Afg3l2 9.25E−44 0.110518283 0.491 0.308 2.30E−39 Ccnd1 9.27E−44 0.130127323 0.144 0.035 2.30E−39 Iigp1 9.65E−44 0.232002466 0.895 0.759 2.40E−39 2810007J24Rik 9.98E−44 −0.118701956 0.988 0.943 2.48E−39 Spcs3 1.06E−43 0.129856927 0.472 0.283 2.63E−39 Psmc5 1.09E−43 0.135453234 0.64 0.441 2.70E−39 Cyp4a10 1.35E−43 −0.289941035 0.614 0.657 3.36E−39 Fbxo21 1.42E−43 −0.200640929 0.249 0.298 3.53E−39 Gm5424 1.63E−43 −0.137211896 0.345 0.3 4.05E−39 Hrsp12 1.75E−43 −0.156961195 0.98 0.939 4.33E−39 H2-D1 1.78E−43 0.167536811 0.916 0.774 4.42E−39 Slc35a3 1.90E−43 0.117116355 0.424 0.246 4.71E−39 Cpn1 1.94E−43 0.146334172 0.84 0.665 4.82E−39 Dpp4 2.07E−43 0.102369468 0.583 0.394 5.14E−39 Chdh 2.26E−43 0.1451577 0.587 0.392 5.62E−39 Bche 2.49E−43 0.162843566 0.566 0.369 6.18E−39 Gas2 2.51E−43 0.142777263 0.55 0.358 6.24E−39 Slc22a1 2.62E−43 −0.199196167 0.777 0.747 6.51E−39 Tpp2 2.79E−43 0.101764106 0.354 0.19 6.93E−39 Skp1a 2.88E−43 0.172529381 0.791 0.606 7.14E−39 Got2 3.06E−43 0.104352218 0.823 0.644 7.60E−39 G3bp2 3.51E−43 0.126428906 0.551 0.359 8.71E−39 Rps8 3.56E−43 −0.118925202 0.545 0.471 8.84E−39 Usp24 3.81E−43 0.11323894 0.436 0.255 9.46E−39 Csnk1a1 3.98E−43 0.136356879 0.64 0.443 9.89E−39 Slc20a2 4.01E−43 0.110778719 0.383 0.215 9.96E−39 Igf2r 4.28E−43 0.102105026 0.32 0.164 1.06E−38 Dazap2 4.28E−43 −0.101392856 0.536 0.472 1.06E−38 Rrp1 5.42E−43 0.103292166 0.511 0.327 1.35E−38 Gucd1 5.48E−43 −0.1039149 0.581 0.511 1.36E−38 Tspo 5.70E−43 −0.171115456 0.532 0.506 1.42E−38 Pgrmc1 5.75E−43 0.159063843 0.99 0.94 1.43E−38 Vps35 7.21E−43 0.105568566 0.509 0.329 1.79E−38 Stt3b 7.63E−43 0.102410897 0.518 0.335 1.90E−38 Ssu72 7.77E−43 −0.112771136 0.553 0.487 1.93E−38 Mmadhc 8.60E−43 0.108169821 0.471 0.288 2.13E−38 Cyp3a13 8.99E−43 0.148503232 0.759 0.569 2.23E−38 Chp1 9.73E−43 0.142681268 0.709 0.515 2.42E−38 Cyp2c44 9.92E−43 0.164710905 0.863 0.698 2.46E−38 Adi1 1.04E−42 0.117291753 0.611 0.419 2.59E−38 Aco1 1.14E−42 0.123631223 0.714 0.525 2.83E−38 Gng12 1.16E−42 0.103486756 0.44 0.265 2.88E−38 Akr1a1 1.27E−42 −0.118556816 0.919 0.857 3.16E−38 Prdx5 1.31E−42 −0.145867251 0.878 0.834 3.26E−38 Pex16 1.59E−42 −0.131815455 0.466 0.416 3.94E−38 Arhgap5 1.80E−42 0.146393752 0.651 0.454 4.47E−38 1810022K09Rik 1.90E−42 −0.180096346 0.286 0.301 4.71E−38 1600014C10Rik 2.28E−42 −0.120294622 0.517 0.462 5.66E−38 Slc39a4 2.34E−42 0.13395424 0.479 0.293 5.81E−38 Sirt3 3.06E−42 −0.139298161 0.45 0.413 7.61E−38 2810428I15Rik 3.07E−42 −0.101899359 0.418 0.349 7.62E−38 Krtcap2 3.08E−42 0.101091751 0.488 0.308 7.65E−38 Abca3 3.23E−42 0.102981662 0.338 0.179 8.03E−38 Samm50 3.43E−42 0.131598944 0.534 0.341 8.51E−38 Tax1bp1 3.59E−42 0.11382647 0.784 0.601 8.93E−38 Klf9 3.63E−42 0.100500247 0.709 0.52 9.01E−38 Fam120a 4.13E−42 0.130340244 0.582 0.391 1.03E−37 Sidt2 4.22E−42 0.110437187 0.395 0.223 1.05E−37 Sec16a 4.49E−42 0.125833914 0.382 0.211 1.11E−37 Akr1d1 4.73E−42 −0.121611839 0.563 0.515 1.17E−37 Kcnk5 5.02E−42 −0.168374452 0.107 0.173 1.25E−37 Cab39l 5.15E−42 0.116519219 0.515 0.331 1.28E−37 D10Jhu81e 5.21E−42 −0.132961769 0.618 0.564 1.29E−37 Shmt2 5.37E−42 −0.116891554 0.533 0.465 1.33E−37 Selenbp1 5.64E−42 −0.185040969 0.725 0.699 1.40E−37 Srp72 6.51E−42 0.123323755 0.651 0.461 1.62E−37 Car5a 6.86E−42 −0.117324599 0.371 0.331 1.70E−37 Snrpd2 7.08E−42 −0.105764256 0.292 0.236 1.76E−37 Rpl3 7.86E−42 −0.104783236 0.402 0.332 1.95E−37 Sec61a1 8.15E−42 0.141299735 0.67 0.476 2.02E−37 Scarb1 8.93E−42 0.134417249 0.549 0.358 2.22E−37 Rbpms 9.27E−42 0.105037375 0.389 0.222 2.30E−37 Psmb3 9.93E−42 −0.12442445 0.398 0.345 2.47E−37 Fkbp3 1.11E−41 −0.113911562 0.366 0.323 2.75E−37 Cox6a1 1.30E−41 −0.131489256 0.939 0.887 3.23E−37 Fetub 1.39E−41 0.174405959 0.859 0.703 3.46E−37 Slc25a44 1.50E−41 0.10239118 0.397 0.228 3.72E−37 Tor1aip2 1.59E−41 0.114296102 0.573 0.386 3.94E−37 Adk 1.76E−41 0.127467378 0.967 0.86 4.37E−37 Gpr146 2.17E−41 0.107393278 0.482 0.305 5.40E−37 Rxra 2.21E−41 0.116073514 0.759 0.574 5.50E−37 Cox8a 2.28E−41 0.176195798 0.796 0.621 5.66E−37 Cct6a 2.40E−41 0.104052442 0.586 0.399 5.95E−37 Anpep 2.60E−41 0.100416126 0.32 0.166 6.47E−37 Ei24 3.14E−41 0.127457502 0.672 0.48 7.79E−37 Mrpl20 3.63E−41 −0.109230853 0.565 0.489 9.02E−37 Serping1 3.66E−41 0.153322882 0.963 0.87 9.09E−37 Srp9 3.97E−41 −0.160772329 0.333 0.336 9.85E−37 Tpr 4.36E−41 0.117035633 0.521 0.339 1.08E−36 Sos1 4.75E−41 0.105944408 0.385 0.221 1.18E−36 Cox7a2 5.09E−41 −0.139135338 0.858 0.784 1.26E−36 Tm9sf3 5.60E−41 0.118956421 0.765 0.582 1.39E−36 Lyrm5 5.81E−41 −0.128193124 0.422 0.396 1.44E−36 Sucla2 5.85E−41 0.115777694 0.727 0.544 1.45E−36 2410015M20Rik 5.99E−41 −0.169256363 0.635 0.604 1.49E−36 Gstt2 6.55E−41 −0.190732451 0.397 0.404 1.63E−36 Cdk2ap2 7.14E−41 −0.131121465 0.273 0.272 1.77E−36 Pglyrp2 7.14E−41 0.150653064 0.607 0.414 1.77E−36 Apof 7.15E−41 0.13917521 0.98 0.897 1.78E−36 Hsd17b7 7.52E−41 0.132910173 0.538 0.353 1.87E−36 Mug2 9.79E−41 0.179746266 0.887 0.738 2.43E−36 Rpl22 9.89E−41 −0.10259468 0.556 0.47 2.46E−36 Rpl32 1.11E−40 −0.190948597 0.8 0.757 2.75E−36 Sptan1 1.11E−40 0.102152857 0.37 0.21 2.76E−36 Selt 1.12E−40 0.141954072 0.694 0.503 2.77E−36 Psmb6 1.12E−40 −0.131951208 0.747 0.683 2.78E−36 Ghitm 1.13E−40 0.129508966 0.891 0.737 2.80E−36 Rps10 1.16E−40 −0.13253262 0.518 0.453 2.87E−36 Copb2 1.67E−40 0.122594343 0.661 0.471 4.16E−36 Dnajb9 1.69E−40 0.120160928 0.416 0.241 4.19E−36 Wnk1 2.04E−40 0.10779068 0.392 0.227 5.08E−36 Cyr61 2.07E−40 0.122951564 0.242 0.102 5.14E−36 Rnaseh2c 2.14E−40 −0.112974422 0.445 0.387 5.30E−36 Pltp 2.46E−40 0.112739945 0.156 0.045 6.10E−36 Abcf1 3.56E−40 0.117230118 0.501 0.315 8.83E−36 PrpfS 3.62E−40 0.112914767 0.505 0.331 8.98E−36 Tmem106b 3.79E−40 0.153891421 0.743 0.557 9.40E−36 Eva1a 3.89E−40 −0.125757849 0.528 0.47 9.67E−36 Hmgcl 4.81E−40 −0.133535955 0.793 0.729 1.19E−35 Tomm70a 4.81E−40 0.151256378 0.685 0.494 1.20E−35 Mettl20 6.82E−40 −0.163343248 0.311 0.327 1.69E−35 Hibch 9.07E−40 −0.123582904 0.455 0.407 2.25E−35 Sacm1l 9.38E−40 0.102054913 0.457 0.29 2.33E−35 Itgb1 1.10E−39 0.121718186 0.651 0.464 2.73E−35 Lactb 1.22E−39 −0.118616118 0.454 0.403 3.03E−35 Gadd45b 1.23E−39 −0.219990566 0.254 0.291 3.07E−35 Eif5 1.26E−39 −0.133564962 0.812 0.74 3.14E−35 S100a10 1.29E−39 −0.177702028 0.676 0.662 3.20E−35 Ptprd 1.41E−39 0.125532384 0.605 0.42 3.51E−35 Chuk 1.66E−39 0.125058676 0.607 0.421 4.11E−35 Mtbfd1 1.75E−39 0.10691059 0.722 0.546 4.35E−35 Abcb11 1.83E−39 0.127231815 0.926 0.791 4.55E−35 Etfb 2.14E−39 −0.13767417 0.977 0.94 5.31E−35 Hspe1 2.30E−39 −0.157908691 0.6 0.557 5.72E−35 Rpl23 2.35E−39 −0.141561405 0.453 0.403 5.84E−35 Htatip2 2.57E−39 −0.152544453 0.334 0.329 6.38E−35 1110001A16Rik 3.27E−39 −0.11299875 0.212 0.208 8.12E−35 Sqrdl 3.48E−39 0.125432563 0.674 0.488 8.64E−35 Rbp4 3.69E−39 −0.134223218 1 0.999 9.15E−35 Crls1 3.80E−39 −0.102433805 0.288 0.263 9.45E−35 Echs1 3.85E−39 −0.101419752 0.89 0.817 9.55E−35 Sqstm1 4.10E−39 0.16784685 0.923 0.805 1.02E−34 Ndufb3 4.24E−39 −0.145234718 0.47 0.43 1.05E−34 Atp11c 4.50E−39 0.107408002 0.76 0.587 1.12E−34 Pitpnb 4.52E−39 0.101346214 0.568 0.393 1.12E−34 Dlst 5.28E−39 0.119678303 0.694 0.512 1.31E−34 Rrbp1 5.94E−39 0.147797245 0.904 0.768 1.47E−34 Ndufa7 6.00E−39 −0.18650272 0.739 0.718 1.49E−34 Pcx 7.57E−39 0.127735069 0.828 0.661 1.88E−34 Ubr3 1.07E−38 0.107986329 0.587 0.41 2.65E−34 Canx 1.12E−38 0.163661783 0.941 0.835 2.79E−34 Mlxipl 1.54E−38 −0.103437041 0.354 0.298 3.82E−34 Slc9a3r1 1.55E−38 0.120027637 0.668 0.483 3.85E−34 Mrpl42 1.70E−38 −0.126024897 0.412 0.386 4.23E−34 Gdi2 1.73E−38 0.15496797 0.782 0.605 4.30E−34 Sphk2 2.01E−38 −0.107275977 0.209 0.188 4.99E−34 Sucnr1 2.78E−38 −0.171877738 0.101 0.201 6.91E−34 Cyp4f14 3.07E−38 0.122432234 0.773 0.6 7.63E−34 Rab7 4.15E−38 0.115589878 0.583 0.402 1.03E−33 Zfyve21 5.89E−38 −0.129446613 0.227 0.245 1.46E−33 1500017E21Rik 6.12E−38 −0.116910818 0.52 0.476 1.52E−33 Pfdn5 6.30E−38 −0.104229394 0.579 0.511 1.57E−33 C130074G19Rik 6.57E−38 −0.139536015 0.476 0.439 1.63E−33 Cpox 6.95E−38 0.109354164 0.628 0.45 1.73E−33 Smlr1 9.30E−38 −0.143751976 0.327 0.314 2.31E−33 Mgea5 9.46E−38 0.115140568 0.436 0.268 2.35E−33 Mrpl14 9.59E−38 −0.133065855 0.567 0.523 2.38E−33 150001 1K16Rik 9.85E−38 −0.156897838 0.297 0.312 2.45E−33 Lonp1 1.03E−37 0.11924964 0.65 0.468 2.56E−33 Ube2h 1.08E−37 −0.109697361 0.257 0.228 2.69E−33 Smg1 1.16E−37 0.102024606 0.24 0.106 2.89E−33 Slc37a4 1.47E−37 0.154508476 0.687 0.502 3.66E−33 Hfe2 1.73E−37 −0.100511022 0.332 0.301 4.29E−33 Dgcr6 2.21E−37 −0.112390889 0.423 0.373 5.50E−33 Sfxn1 3.26E−37 0.177292254 0.68 0.496 8.10E−33 Churc1 4.30E−37 −0.112101868 0.199 0.186 1.07E−32 Mrpl27 4.60E−37 −0.130784318 0.287 0.275 1.14E−32 Hadha 4.81E−37 0.125402769 0.888 0.744 1.19E−32 Ubxn1 5.35E−37 −0.107380689 0.655 0.57 1.33E−32 Abca8a 6.50E−37 0.112860383 0.442 0.277 1.61E−32 Entpd5 6.69E−37 −0.114063163 0.647 0.578 1.66E−32 1110065P20Rik 6.85E−37 −0.110034234 0.3 0.273 1.70E−32 Uqcrh 7.79E−37 −0.146211767 0.861 0.81 1.93E−32 Emg1 9.41E−37 −0.106005411 0.369 0.325 2.34E−32 Dld 9.96E−37 0.10036701 0.627 0.451 2.47E−32 Cml2 1.19E−36 0.14309935 0.957 0.857 2.96E−32 Tmem176a 1.24E−36 0.129581291 0.612 0.429 3.08E−32 Acox2 1.32E−36 0.125739523 0.696 0.517 3.28E−32 Hmgcr 1.98E−36 0.106466986 0.435 0.272 4.91E−32 Mrps24 2.00E−36 −0.139387979 0.608 0.566 4.96E−32 Slc25a13 2.05E−36 0.118116385 0.819 0.655 5.09E−32 Rpl18 2.11E−36 −0.114603362 0.313 0.266 5.24E−32 Smagp 2.11E−36 −0.108071023 0.23 0.209 5.25E−32 Psmb5 2.24E−36 −0.125235705 0.395 0.348 5.55E−32 Serpinf2 2.74E−36 0.121084682 0.953 0.843 6.81E−32 Slc25a23 2.79E−36 0.113100224 0.572 0.399 6.92E−32 Eif3c 3.08E−36 0.102123395 0.715 0.541 7.64E−32 Rplp0 3.22E−36 −0.152097782 0.828 0.791 8.00E−32 Rnf181 3.86E−36 −0.118990143 0.35 0.318 9.59E−32 Dnajc3 3.88E−36 0.122737182 0.906 0.772 9.64E−32 Sdf2 4.05E−36 −0.108593657 0.301 0.279 1.00E−31 Tsc22d3 4.47E−36 −0.117456945 0.326 0.312 1.11E−31 Rplp1 4.72E−36 −0.196523046 0.782 0.757 1.17E−31 Ifi27 4.81E−36 0.228184801 0.632 0.453 1.19E−31 Mrpl18 5.29E−36 −0.106603574 0.391 0.343 1.31E−31 Ube2b 5.62E−36 0.140018225 0.657 0.478 1.39E−31 Gpx4 6.41E−36 −0.101573086 0.301 0.25 1.59E−31 Mrpl33 7.02E−36 −0.105537953 0.471 0.419 1.74E−31 Ssr4 7.96E−36 −0.131894778 0.736 0.687 1.98E−31 Naprt1 8.70E−36 −0.112711561 0.56 0.492 2.16E−31 Hsp90ab1 9.49E−36 0.137555293 0.982 0.922 2.36E−31 Hsd17b12 1.08E−35 0.150192807 0.811 0.647 2.69E−31 Smdt1 1.45E−35 −0.136251907 0.623 0.573 3.59E−31 1100001G20Rik 1.79E−35 −0.181522579 0.998 0.982 4.44E−31 Pxdc1 1.82E−35 −0.133589092 0.345 0.333 4.53E−31 Gm11273 2.05E−35 −0.154535944 0.034 0.102 5.09E−31 1110001J03Rik 3.16E−35 −0.131166164 0.498 0.456 7.84E−31 Cald1 3.35E−35 0.130849221 0.889 0.749 8.32E−31 Lsmd1 3.46E−35 −0.107665711 0.404 0.357 8.59E−31 Snord118 3.53E−35 0.102458085 0.401 0.248 8.78E−31 Gnpnat1 3.96E−35 −0.102162123 0.309 0.279 9.84E−31 H2afv 5.34E−35 −0.108111525 0.291 0.275 1.33E−30 Hspa8 5.38E−35 0.148342283 0.889 0.756 1.34E−30 Stard5 6.66E−35 −0.106226141 0.351 0.315 1.65E−30 Cyp2d9 6.68E−35 −0.10468367 0.997 0.959 1.66E−30 Atf4 1.03E−34 0.170664039 0.622 0.442 2.56E−30 Cluh 1.34E−34 0.10709751 0.801 0.641 3.32E−30 Tmem56 1.51E−34 0.130642059 0.779 0.612 3.75E−30 Rps9 1.57E−34 −0.160672445 0.733 0.675 3.89E−30 Rnf213 2.52E−34 0.120260244 0.258 0.123 6.25E−30 Fam162a 2.59E−34 −0.115030119 0.595 0.53 6.43E−30 Oplah 2.74E−34 0.10196367 0.626 0.455 6.81E−30 Dhrs4 3.20E−34 −0.115542613 0.773 0.69 7.96E−30 2310001H17Rik 3.22E−34 −0.145935249 0.163 0.212 8.00E−30 Anapc13 3.37E−34 −0.103891949 0.501 0.427 8.38E−30 2810459M11Rik 3.87E−34 −0.128519254 0.303 0.298 9.60E−30 Mrpl11 4.74E−34 −0.11725047 0.376 0.345 1.18E−29 Irf6 5.40E−34 −0.108059035 0.212 0.214 1.34E−29 Slc25a3 6.95E−34 0.149859347 0.89 0.758 1.73E−29 Rpl13 8.40E−34 −0.102068358 0.536 0.464 2.09E−29 Rpl13a-ps1 9.43E−34 −0.136090818 0.03 0.102 2.34E−29 Pnpla8 1.02E−33 0.125201153 0.715 0.544 2.54E−29 Camk1d 1.06E−33 0.130256351 0.405 0.247 2.64E−29 Pa2g4 1.17E−33 0.112190082 0.589 0.418 2.90E−29 Txn1 1.37E−33 −0.116589612 0.869 0.809 3.41E−29 Serf2 1.38E−33 −0.102114553 0.271 0.237 3.43E−29 Arrdc3 1.74E−33 −0.1460998 0.208 0.213 4.32E−29 Ephx1 1.80E−33 −0.102641923 0.874 0.8 4.48E−29 Sgpl1 1.84E−33 −0.102012642 0.344 0.3 4.57E−29 mt-Ti 1.95E−33 −0.175221151 0.091 0.167 4.85E−29 Chac2 2.43E−33 −0.116526774 0.25 0.251 6.03E−29 Gm2000 2.73E−33 −0.101274241 0.168 0.137 6.77E−29 Rnf11 2.96E−33 0.115434821 0.646 0.476 7.36E−29 Etnppl 3.39E−33 0.199542145 0.769 0.606 8.41E−29 Sdr42e1 3.62E−33 −0.10244655 0.411 0.363 8.99E−29 Fahd1 3.64E−33 −0.119584582 0.287 0.272 9.03E−29 Krt18 3.68E−33 0.185376047 0.771 0.617 9.15E−29 Cstf3 5.02E−33 −0.130987349 0.128 0.186 1.25E−28 Alkbh7 5.19E−33 −0.126292957 0.202 0.215 1.29E−28 Srp14 5.79E−33 −0.103296322 0.396 0.359 1.44E−28 Etfdh 1.05E−32 0.125403001 0.847 0.7 2.61E−28 Acaa2 1.17E−32 0.112138898 0.996 0.96 2.91E−28 Mxd4 1.19E−32 −0.100169237 0.358 0.321 2.96E−28 F9 1.37E−32 0.120261398 0.791 0.632 3.41E−28 H2-Q10 1.94E−32 0.109441992 1 0.982 4.83E−28 Mup20 2.37E−32 −0.244695365 1 1 5.87E−28 Mcfd2 2.42E−32 0.109751379 0.798 0.643 6.00E−28 Ugt3a2 2.43E−32 0.110842492 0.836 0.689 6.04E−28 Slc19a2 2.66E−32 −0.105653788 0.315 0.293 6.61E−28 Cox5b 2.83E−32 −0.184963493 0.747 0.726 7.02E−28 C6 4.05E−32 0.126254945 0.798 0.642 1.01E−27 Psmb4 5.34E−32 −0.1235222 0.764 0.705 1.33E−27 Gm2788 5.45E−32 −0.119044189 0.279 0.264 1.35E−27 Cyp2d10 5.96E−32 −0.114162001 0.958 0.921 1.48E−27 Bcar3 6.99E−32 −0.154603512 0.132 0.193 1.74E−27 Wdr89 7.20E−32 −0.157854036 0.08 0.118 1.79E−27 Polr2f 1.08E−31 −0.10168269 0.363 0.321 2.68E−27 Gm16157 1.10E−31 −0.100720355 0.215 0.197 2.73E−27 Immp1l 1.14E−31 −0.117878413 0.317 0.313 2.83E−27 Lect2 1.87E−31 −0.274252442 0.297 0.414 4.64E−27 Acsl1 2.77E−31 −0.149382996 0.958 0.924 6.89E−27 Maob 3.15E−31 0.107182064 0.734 0.575 7.82E−27 Gm6484 3.49E−31 0.123791929 0.314 0.174 8.67E−27 Ybx1 4.79E−31 −0.108005701 0.685 0.605 1.19E−26 Pla2g12b 6.31E−31 −0.10068138 0.517 0.463 1.57E−26 Pithd1 6.72E−31 −0.101630538 0.177 0.184 1.67E−26 1810009A15Rik 7.82E−31 −0.105379118 0.227 0.218 1.94E−26 Hnrnpa2b1 7.98E−31 0.119047009 0.86 0.722 1.98E−26 Tecr 9.10E−31 0.101458193 0.647 0.486 2.26E−26 Ddt 1.69E−30 −0.172944365 0.847 0.829 4.20E−26 Ccl9 1.84E−30 −0.101196684 0.534 0.486 4.57E−26 Gm13773 2.84E−30 −0.13782302 0.047 0.11 7.05E−26 Tubb5 3.08E−30 −0.118258355 0.276 0.271 7.64E−26 Gm11789 3.31E−30 −0.107724995 0.235 0.228 8.22E−26 Rps21 4.02E−30 −0.113921701 0.651 0.579 9.98E−26 Slc40a1 4.18E−30 −0.111681574 0.353 0.328 1.04E−25 Ide 4.60E−30 −0.128451427 0.524 0.494 1.14E−25 Urah 5.21E−30 −0.109034054 0.911 0.852 1.29E−25 1500012F01Rik 6.40E−30 −0.116078802 0.2 0.205 1.59E−25 Cml5 1.19E−29 −0.124698142 0.151 0.178 2.94E−25 Cenpv 1.47E−29 −0.10852708 0.222 0.21 3.64E−25 Sh3bp5 1.70E−29 −0.131584862 0.191 0.21 4.22E−25 Lsr 1.70E−29 0.118122924 0.677 0.517 4.22E−25 Hsd17b10 1.71E−29 −0.114042727 0.759 0.7 4.25E−25 Acadvl 1.87E−29 0.126009037 0.9 0.783 4.65E−25 Creb3l3 1.90E−29 0.124229468 0.93 0.831 4.71E−25 Gm10275 2.32E−29 −0.131334292 0.068 0.126 5.76E−25 Ptms 2.41E−29 0.110348643 0.831 0.689 5.99E−25 Cyp2c68 3.17E−29 −0.113343173 0.593 0.558 7.87E−25 Cyp4v3 5.18E−29 0.136434082 0.932 0.827 1.29E−24 Sod2 6.44E−29 0.100502591 0.828 0.687 1.60E−24 Hjurp 7.95E−29 −0.138156531 0.223 0.219 1.97E−24 Saa3 8.86E−29 0.298054041 0.195 0.087 2.20E−24 C8b 9.77E−29 0.113345886 0.963 0.881 2.43E−24 Ctsz 1.05E−28 0.125462706 0.789 0.641 2.60E−24 Hdhd3 1.06E−28 −0.120077709 0.172 0.201 2.63E−24 Rpl31 2.64E−28 −0.114404945 0.166 0.16 6.54E−24 Paqr7 3.16E−28 −0.115007751 0.144 0.159 7.84E−24 Bola3 5.01E−28 −0.115283165 0.574 0.525 1.24E−23 Oat 5.60E−28 −0.255537891 0.502 0.611 1.39E−23 Serpina12 6.30E−28 0.135573206 0.648 0.492 1.56E−23 Csad 9.84E−28 0.204004276 0.872 0.744 2.44E−23 Slc46a3 1.39E−27 −0.111772252 0.203 0.211 3.44E−23 Sdhaf1 5.54E−27 −0.10322437 0.113 0.138 1.37E−22 Rgn 6.33E−27 −0.13339713 0.807 0.874 1.57E−22 Tyw5 1.29E−26 −0.115955707 0.141 0.161 3.20E−22 Bok 1.52E−26 −0.107596384 0.062 0.111 3.78E−22 Nr2f2 3.29E−26 −0.135717133 0.11 0.163 8.16E−22 Clec2h 1.15E−25 −0.120494736 0.059 0.126 2.85E−21 Ebp 2.12E−25 0.120141088 0.801 0.666 5.25E−21 Aldh2 2.19E−25 0.108487481 0.994 0.973 5.44E−21 Ctsc 8.47E−25 0.12557031 0.413 0.271 2.10E−20 Apoh 1.17E−24 −0.113138266 0.997 0.986 2.91E−20 mmu-mir-6240 3.74E−24 −0.197588471 0.054 0.115 9.29E−20 Mrap 5.13E−24 0.100266553 0.408 0.272 1.27E−19 9030616G12Rik 8.16E−23 −0.113944704 0.075 0.126 2.03E−18 Serpina1a 1.69E−22 −0.130631577 0.998 0.991 4.20E−18 Car3 2.72E−22 −0.118093283 0.999 0.974 6.75E−18 Cox5a 4.36E−22 0.119858632 0.822 0.702 1.08E−17 Pigr 6.75E−22 0.116709563 0.988 0.947 1.68E−17 Dlc1 2.09E−21 −0.12318528 0.1 0.148 5.18E−17 Cyp7a1 2.57E−21 −0.191761184 0.186 0.259 6.39E−17 Gulo 1.21E−20 −0.161523894 0.482 0.497 2.99E−16 Cyp26a1 2.63E−18 −0.115338737 0.155 0.184 6.52E−14 Acaa1a 7.70E−18 −0.106217042 0.735 0.679 1.91E−13 Fitm1 5.83E−16 −0.136552777 0.175 0.208 1.45E−11 Fam13a 3.40E−14 −0.101488514 0.102 0.118 8.43E−10 Cyp4a14 1.89E−13 0.136365312 0.541 0.431 4.70E−09 Gnmt 1.77E−10 −0.105899231 0.999 0.988 4.39E−06 Trf 6.06E−10 −0.106899897 0.999 1 1.51E−05 Aldh3a2 6.02E−09 −0.141606596 0.454 0.529 0.000149421 Mup7 0.007918627 −0.293978105 0.998 0.998 1 Hamp 0.31057435 0.10479673 0.888 0.884 1

TABLE 5b Differentially expressed genes between time point PHX3 FC.2 and untreated (UT). p_val avg_logFC pct.1 pct.2 p_val_adj Saa2 0 2.971862499 0.999 0.222 0 Mt1 0 2.610854994 1 0.556 0 Mt2 0 2.6060431 1 0.365 0 Saa1 0 2.202156726 1 0.662 0 Steap4 0 1.890015167 0.973 0.222 0 Serpina3n 0 1.759758939 0.992 0.574 0 Lcn2 0 1.499141183 0.815 0.07 0 Lpin1 0 1.327657625 0.94 0.31 0 n-R5-8s1 0 1.289598504 0.805 0.031 0 Igfbp1 0 1.288789902 0.99 0.717 0 Cxcl1 0 1.230398019 0.919 0.314 0 Scd1 0 1.081676999 0.998 0.901 0 Gm26924 0 1.063463323 1 1 0 Il1r1 0 0.998168131 0.8 0.167 0 Fga 0 0.981249724 1 0.997 0 Gm24601 0 0.924568273 0.661 0.015 0 Nnmt 0 0.901052904 0.97 0.716 0 Itih4 0 0.887186241 0.999 0.948 0 St3gal5 0 0.882761517 0.915 0.49 0 Tacc2 0 0.877623973 0.707 0.071 0 Lrg1 0 0.870250525 0.981 0.736 0 Fam134b 0 0.865578177 0.876 0.405 0 Tat 0 0.857965136 0.998 0.903 0 Saa4 0 0.854921603 0.981 0.749 0 Thrsp 0 0.836598219 0.98 0.627 0 Slc39a14 0 0.831584936 0.849 0.343 0 Lars2 0 0.816795688 1 0.994 0 Fgg 0 0.809322713 1 0.991 0 Slc38a2 0 0.797899442 0.874 0.413 0 Serpina3m 0 0.779052745 0.961 0.722 0 Hp 0 0.774785279 1 0.999 0 Fgb 0 0.739519125 1 1 0 Gm15564 0 0.735157137 0.999 0.956 0 Serpina10 0 0.733655099 0.934 0.641 0 Plin2 0 0.720463076 0.952 0.714 0 Aass 0 0.705615345 0.965 0.716 0 Fmo5 0 0.690160801 0.991 0.837 0 Fn1 0 0.684266092 0.983 0.821 0 Fkbp5 0 0.663304836 0.665 0.117 0 Slc25a47 0 0.635928777 0.994 0.927 0 Mat1a 0 0.623734998 0.999 0.966 0 Aldob 0 0.490200848 1 0.996 0 Mup3 0 −0.526410044 1 1 0 Cyb5 0 −0.71965743 0.992 0.983 0 mt-Rnr1 0 −0.872186844 1 1 0 mt-Rnr2 0 −0.873557854 1 1 0 Mup11 0 −0.976755523 0.996 1 0 mt-Nd2 0 −1.128776891 0.996 0.999 0 mt-Nd1 0 −1.136736863 0.999 1 0 mt-Nd5 0 −1.145550707 0.974 0.995 0 mt-Co3 0 −1.233961828 0.106 0.603 0 Gm13775 0 −1.255657303 0.205 0.761 0 mt-Cytb 0 −1.296043506 0.993 0.999 0 mt-Co2 0 −1.341686736 0.1 0.629 0 mt-Co1 0 −1.381307687 0.986 0.999 0 mt-Nd4 0 −1.630375247 0.977 0.998 0 Mup4 0 −1.805301681 0.374 0.898 0 Mup6 0 −2.386597202 0.714 0.992 0 Mup9 0 −2.453596744 0.401 0.976 0 Mup17 0 −2.514472885 0.899 1 0 Mup18 0 −2.617739049 0.547 0.997 0 Mup19 0 −2.932276479 0.84 1 0 Acox1 1.48219693752374e−323 0.540022158 0.998 0.966 3.68059143525895e−319 Hnf4a 5.92878775009496e−323 0.644195253 0.969 0.743 1.47223657410358e−318 B3galt1 1.64029794419294e−321 0.788734938 0.634 0.163  4.0731878550199e−317 Cyp2b10 2.20501497738948e−320 −1.254972098 0.132 0.542 5.47549319185356e−316 Mup5 4.03503412958546e−319 −1.484560547 0.52 0.839 1.00197967505866e−314 H3f3b 7.69670285060869e−319 0.755567107 0.831 0.419 1.91124525186315e−314 Btg2  6.7929354703014e−310 0.772686832 0.708 0.241  1.69E−305 Sephs2 7.26878065222103e−310 0.618707003 0.974 0.761  1.80E−305 Ankrd55  1.43E−296 −1.464696038 0.374 0.696  3.54E−292 Hspb8  1.52E−295 0.667847253 0.914 0.597  3.78E−291 Slc7a2  4.69E−288 0.622326529 0.964 0.735  1.17E−283 Cldn14  8.97E−284 0.511583526 0.505 0.076  2.23E−279 C3  4.33E−282 0.482674202 0.999 0.99  1.07E−277 Gjb2  5.86E−278 0.639507436 0.901 0.572  1.46E−273 Rcan1  1.11E−277 0.509239866 0.522 0.085  2.75E−273 Errfi1  7.45E−268 0.500850526 0.998 0.911  1.85E−263 Pfkfb3  1.00E−265 0.426580733 0.421 0.039  2.50E−261 Arhgef26  1.50E−264 0.568544702 0.67 0.203  3.71E−260 Cyp2c29  3.44E−262 −1.027267705 0.751 0.93  8.53E−258 Egfr  8.47E−255 0.555834247 0.989 0.809  2.10E−250 Gsta3  1.25E−250 −0.53784222 0.993 0.956  3.11E−246 Bcl3  1.67E−248 0.419650143 0.479 0.074  4.14E−244 Snx10  3.08E−247 0.558244633 0.63 0.188  7.65E−243 Pck1  7.20E−247 0.43447474 0.999 0.987  1.79E−242 Mup16  3.02E−246 −0.848726713 0.816 0.934  7.49E−242 Bach1  1.01E−243 0.533237374 0.589 0.151  2.51E−239 Tifa  8.52E−243 0.392339477 0.393 0.036  2.12E−238 Hpx  7.87E−242 0.460272423 1 0.997  1.95E−237 Ugt2b5  6.48E−241 −0.423085187 0.991 0.959  1.61E−236 Etnk2  2.21E−240 0.592353201 0.918 0.655  5.48E−236 2010003K11Rik  8.37E−239 0.372219971 0.412 0.046  2.08E−234 Rapgef4  8.03E−238 0.588317735 0.836 0.436  1.99E−233 Tiparp  5.00E−233 0.489122153 0.485 0.087  1.24E−228 Gpt2  2.89E−230 0.533331785 0.949 0.725  7.18E−226 Slc25a25  6.62E−227 0.544465891 0.945 0.704  1.64E−222 Mup10  6.77E−224 0.428268029 0.965 0.692  1.68E−219 Txnip  3.37E−223 0.552612237 0.741 0.297  8.37E−219 Cyp2c50  9.25E−220 −0.763912176 0.693 0.888  2.30E−215 Xbp1  2.56E−219 0.539986 0.89 0.57  6.35E−215 Upp2  4.48E−218 0.541753512 0.934 0.673  1.11E−213 Mfsd2a  1.49E−217 0.496351884 0.563 0.148  3.69E−213 Actb  1.79E−216 0.456981443 0.99 0.886  4.44E−212 mmu-mir-6236  6.91E−215 0.468866739 0.989 0.837  1.72E−210 Fbf1  1.36E−212 0.298573909 0.336 0.027  3.38E−208 Hsd3b5  1.76E−209 −0.587528886 0.49 0.587  4.36E−205 Trib1  2.60E−209 0.581754281 0.705 0.308  6.45E−205 Arg1  4.87E−205 0.381616351 1 0.982  1.21E−200 Plin5  2.75E−204 0.489257529 0.736 0.315  6.82E−200 Plk3  4.61E−204 0.488016367 0.644 0.226  1.15E−199 Mup13  1.15E−203 −0.755608269 0.303 0.546  2.86E−199 Mtss1  5.64E−203 0.552137981 0.812 0.454  1.40E−198 Klf6  1.08E−202 0.3616937 0.346 0.034  2.69E−198 Itih3  6.73E−202 0.469631651 0.988 0.89  1.67E−197 Gm23935  3.21E−201 0.498066925 0.999 0.925  7.96E−197 Mup21  2.39E−199 −0.668770594 0.829 0.929  5.93E−195 Adck3  5.76E−199 −0.482940158 0.729 0.764  1.43E−194 Cyp2c54  3.82E−198 −0.712859584 0.491 0.759  9.48E−194 Serpina3c  1.71E−196 −0.554657351 0.118 0.385  4.23E−192 Slc10a2  2.81E−196 0.30563824 0.376 0.05  6.99E−192 Sdc4  3.39E−196 0.43560504 0.986 0.867  8.41E−192 Egr1  3.50E−196 0.620480469 0.79 0.447  8.70E−192 Apcs  4.35E−195 0.573439593 0.854 0.525  1.08E−190 Atf3  8.39E−194 0.597274889 0.56 0.179  2.08E−189 Hsd3b7  1.35E−191 −0.451728474 0.795 0.798  3.36E−187 Orm1  2.91E−190 0.463411533 0.993 0.952  7.24E−186 Pzp  6.72E−190 0.387351113 0.999 0.986  1.67E−185 Glul  9.26E−190 0.478908893 0.58 0.18  2.30E−185 Prg4  6.84E−189 0.480504574 0.585 0.188  1.70E−184 Fgl1  1.44E−188 0.49338252 0.961 0.784  3.57E−184 Gpcpd1  3.50E−188 0.53780646 0.778 0.398  8.70E−184 Klf10  4.90E−188 0.304779554 0.388 0.06  1.22E−183 Rgs16  2.29E−187 0.438105488 0.482 0.113  5.68E−183 Ptp4a1  3.23E−187 0.393137367 0.528 0.145  8.02E−183 mt-Atp6  3.00E−186 −0.852555757 0.138 0.452  7.45E−182 Fam35a  2.25E−184 0.470461753 0.642 0.246  5.59E−180 Rhob  2.93E−184 0.37207281 0.4 0.069  7.28E−180 Mup15  6.78E−184 −1.074409915 0.357 0.617  1.68E−179 Cyp3a25  7.66E−184 −0.41051207 0.928 0.919  1.90E−179 Got1  1.96E−183 0.542891511 0.866 0.587  4.86E−179 Ces1d  6.99E−180 −0.385155368 0.944 0.923  1.74E−175 Shb  1.09E−178 0.430613558 0.589 0.204  2.71E−174 Sds  5.06E−177 0.787094904 0.868 0.67  1.26E−172 Abca1  3.96E−176 0.50506234 0.756 0.377  9.82E−172 1810055G02Rik  7.47E−174 0.382584093 0.528 0.155  1.86E−169 Stat3  9.40E−173 0.460515229 0.701 0.318  2.33E−168 Akr1c6  3.12E−171 −0.43492211 0.992 0.971  7.75E−167 Apoe  6.43E−171 −0.26209828 1 1  1.60E−166 Igfbp4  4.07E−170 0.387861679 0.986 0.866  1.01E−165 Cdkn1a  2.71E−169 0.449325471 0.572 0.195  6.74E−165 Gfra1  5.61E−169 0.474694426 0.835 0.498  1.39E−164 Gc  9.68E−169 0.233764264 1 0.999  2.40E−164 Nrg4  3.42E−168 0.246089001 0.306 0.034  8.49E−164 Ivns1abp  1.34E−166 0.46254094 0.688 0.315  3.32E−162 Fh1  2.21E−165 0.471428771 0.915 0.648  5.48E−161 Myo1e  9.01E−164 0.399456672 0.551 0.182  2.24E−159 Slc41a2  1.15E−163 0.3685439 0.482 0.134  2.86E−159 Mup8  1.92E−163 −0.793731191 0.111 0.373  4.78E−159 Slc25a51  3.30E−163 0.372157664 0.522 0.161  8.21E−159 Psen2  1.62E−162 −0.419555606 0.749 0.774  4.03E−158 Dak  3.36E−162 0.481947664 0.867 0.563  8.34E−158 Apoc4  3.03E−160 −0.356086407 0.999 0.98  7.52E−156 Fasn  1.83E−159 0.467168076 0.719 0.345  4.54E−155 Bhlhe40  9.28E−159 0.403249298 0.628 0.251  2.30E−154 Tmem87b  4.54E−156 0.288330587 0.415 0.096  1.13E−151 Ddx3x  1.61E−155 0.47100162 0.823 0.513  4.00E−151 Ttr  1.71E−155 0.248320061 1 1  4.24E−151 Aldh1a1  6.92E−152 −0.40245097 0.984 0.956  1.72E−147 Slc25a22  2.16E−151 0.390931532 0.649 0.282  5.36E−147 Rnf103  8.20E−150 0.438540394 0.701 0.35  2.04E−145 Scara5  1.55E−149 0.221632911 0.324 0.054  3.85E−145 B4galt1  3.66E−147 0.321380868 0.494 0.155  9.09E−143 Rnf125  1.05E−146 −0.463320018 0.312 0.493  2.62E−142 Hacl1  1.08E−146 −0.332899987 0.842 0.797  2.67E−142 Gm26917  1.95E−145 0.46739621 0.523 0.181  4.85E−141 Junb  2.38E−145 0.458500682 0.788 0.47  5.91E−141 Cps1  3.74E−145 0.336429448 0.999 0.971  9.30E−141 Atp1b1  1.85E−144 0.424801231 0.567 0.226  4.59E−140 Glud1  6.49E−144 0.341724783 0.991 0.905  1.61E−139 D10Wsu102e  2.64E−142 0.256022156 0.338 0.063  6.54E−138 Hyou1  2.91E−142 0.431109873 0.731 0.385  7.23E−138 Jmjd1c  3.12E−142 0.39612601 0.516 0.178  7.75E−138 Apoa5  6.44E−142 0.30259839 0.999 0.974  1.60E−137 4933426M11Rik  8.78E−142 0.28624304 0.419 0.109  2.18E−137 Scp2  3.84E−141 0.279911381 0.997 0.986  9.52E−137 Jun  2.06E−140 0.479246114 0.864 0.593  5.12E−136 Mup12  3.48E−140 −0.589618573 0.792 0.86  8.63E−136 Cyp2a5  3.99E−140 −0.938183249 0.278 0.555  9.91E−136 Cpt1a  7.36E−140 0.42860734 0.894 0.651  1.83E−135 Pik3r1  1.27E−139 0.389193614 0.577 0.231  3.16E−135 Apob  4.15E−139 0.416824707 0.997 0.989  1.03E−134 Epas1  1.69E−136 0.38425941 0.646 0.297  4.19E−132 Ugt2b36  6.78E−136 −0.287193139 0.978 0.93  1.68E−131 Mbd1  2.07E−135 0.348094524 0.507 0.176  5.14E−131 Mup2  5.79E−135 −0.650107006 0.161 0.392  1.44E−130 Foxq1  5.09E−134 0.22551931 0.377 0.096  1.26E−129 Gadd45g  2.13E−133 0.392031882 0.899 0.639  5.28E−129 Fos  5.48E−133 0.524733327 0.785 0.51  1.36E−128 Bcl2l1  6.25E−133 0.280315334 0.426 0.122  1.55E−128 Ptpn1  8.78E−133 0.268263225 0.402 0.107  2.18E−128 Slc25a15  1.87E−132 0.402049896 0.931 0.738  4.63E−128 Tdo2  5.72E−132 0.25156007 0.999 0.991  1.42E−127 Rnd3  2.06E−131 0.285147682 0.375 0.091  5.11E−127 Adh1  2.50E−131 −0.295980789 0.995 0.96  6.22E−127 Gm5096  4.91E−131 −0.399548106 0.364 0.468  1.22E−126 Litaf  5.25E−131 0.396007707 0.603 0.278  1.30E−126 Wbp1l  8.03E−130 0.409138156 0.867 0.606  1.99E−125 Grn  4.87E−129 0.403315761 0.726 0.396  1.21E−124 Tns1  5.97E−129 0.33981795 0.524 0.196  1.48E−124 Cyp2c37  6.92E−129 −0.662335734 0.314 0.608  1.72E−124 Ahcy  1.09E−128 −0.375627724 0.918 0.916  2.71E−124 Foxa3  4.50E−128 0.307992015 0.505 0.182  1.12E−123 Qsox1  5.91E−128 0.378486857 0.925 0.707  1.47E−123 Cth  8.38E−128 −0.308847665 0.898 0.838  2.08E−123 Id2  2.52E−127 0.430147785 0.826 0.579  6.25E−123 Myh9  8.87E−127 0.399128031 0.653 0.318  2.20E−122 Cox6c  5.03E−126 −0.41128283 0.893 0.884  1.25E−121 Raph1  2.97E−125 0.242670968 0.382 0.1  7.38E−121 Ier2  4.45E−123 0.452598264 0.763 0.49  1.10E−118 Cfh  5.44E−123 0.312615767 0.991 0.897  1.35E−118 Itih2  1.39E−122 0.336714211 0.984 0.884  3.45E−118 Rsp14  1.25E−121 −0.346340977 0.936 0.917  3.11E−117 Cyp8b1  1.41E−121 −0.364571013 0.714 0.745  3.50E−117 Ccnl1  1.51E−121 0.341338448 0.526 0.206  3.75E−117 Cox4i1  1.81E−121 −0.288035158 0.992 0.958  4.50E−117 Eef1a1  5.57E−121 0.340768186 0.967 0.85  1.38E−116 Nedd4l  2.65E−120 0.271827098 0.447 0.147  6.58E−116 Inmt  5.73E−120 −0.308364158 0.966 0.884  1.42E−115 Cep85l  1.49E−119 0.202664771 0.347 0.089  3.71E−115 Elovl5  6.23E−119 0.382267188 0.863 0.58  1.55E−114 Zbtb16  6.92E−119 0.232600907 0.414 0.131  1.72E−114 Il17ra  2.85E−118 0.203529938 0.302 0.061  7.08E−114 Hip1r  3.33E−118 0.213858215 0.362 0.098  8.27E−114 Plg  4.13E−118 0.26619661 0.998 0.961  1.03E−113 Eif4g2  6.98E−118 0.384302798 0.905 0.678  1.73E−113 Atg14  1.11E−117 0.231648357 0.369 0.1  2.75E−113 Ppip5k2  1.67E−117 0.30299148 0.51 0.197  4.16E−113 Ulk1  3.53E−117 0.297841785 0.499 0.189  8.77E−113 Pon1  1.04E−116 −0.302819466 0.936 0.906  2.59E−112 Elovl6  1.22E−116 0.37962641 0.553 0.24  3.04E−112 Il6ra  5.95E−116 0.251696836 0.431 0.142  1.48E−111 Ndufb11  4.83E−115 −0.36792318 0.722 0.735  1.20E−110 Igfbp2  3.10E−113 −0.348403589 0.886 0.885  7.70E−109 Fads2  1.76E−112 0.323744791 0.592 0.273  4.37E−108 Tnfrsf1a  2.59E−112 0.346845029 0.551 0.244  6.43E−108 Ugt2b34  3.49E−112 −0.290735843 0.918 0.874  8.65E−108 Gcnt2  3.49E−112 0.221618104 0.333 0.082  8.67E−108 Ell2  5.30E−112 0.371745977 0.72 0.416  1.32E−107 Ly6e  5.39E−112 0.42022985 0.68 0.386  1.34E−107 Rps2  1.20E−110 −0.44250848 0.675 0.757  2.99E−106 Epb4.1  3.29E−110 0.349430673 0.617 0.304  8.16E−106 Ptpn2  1.67E−109 0.225408583 0.354 0.097  4.15E−105 Clpx  6.99E−109 −0.306093278 0.818 0.783  1.74E−104 Zc3h13  8.36E−109 0.204542393 0.325 0.083  2.08E−104 Rps27l  3.68E−108 −0.361138678 0.855 0.849  9.13E−104 Dst  5.39E−108 0.329905553 0.507 0.206  1.34E−103 Atl2  1.06E−107 0.321873809 0.674 0.361  2.64E−103 Gm4076  1.66E−107 −0.342157966 0.007 0.184  4.12E−103 Gm20594  2.54E−107 −0.559577825 0.108 0.294  6.30E−103 Lpgat1  2.69E−107 0.390146943 0.776 0.502  6.68E−103 Hmgcs1  5.90E−107 −0.258009688 0.778 0.703  1.46E−102 Esd  1.57E−106 −0.302906103 0.794 0.784  3.91E−102 Oaz1  2.04E−106 −0.339004868 0.759 0.75  5.06E−102 Pptc7  7.95E−106 0.227095018 0.412 0.141  1.98E−101 Sult1a1  1.09E−105 0.371023537 0.899 0.707  2.72E−101 Nfil3  2.41E−105 0.338730712 0.617 0.309  5.98E−101 Aqp8  3.51E−105 −0.331182913 0.444 0.505  8.71E−101 Gpx1  3.94E−105 −0.222094695 1 0.999  9.79E−101 Cyp3a11  4.68E−105 −0.251219977 0.999 1  1.16E−100 Cml1  2.22E−104 −0.277339974 0.803 0.757  5.50E−100 Apoa4  2.46E−104 0.609214916 0.604 0.339  6.11E−100 Jak1  3.27E−104 0.362766687 0.648 0.342  8.12E−100 Arid5b  4.76E−104 0.232391653 0.472 0.186 1.18E−99 Ralgapa2  2.31E−103 0.20791298 0.334 0.092 5.73E−99 G6pc  4.45E−103 0.341403933 0.948 0.752 1.11E−98 Ifitm3  2.02E−102 0.331673739 0.958 0.812 5.02E−98 Zfp36  2.26E−102 0.407014847 0.776 0.522 5.61E−98 Oaf  5.19E−102 −0.333766768 0.79 0.794 1.29E−97 Mgst1  5.80E−102 −0.322742924 1 0.997 1.44E−97 Uqcrq  9.27E−102 −0.316451873 0.98 0.951 2.30E−97 Garem  4.42E−101 0.204881738 0.351 0.104 1.10E−96 B2m  4.67E−101 0.246889569 0.997 0.963 1.16E−96 Hebp1  2.97E−100 −0.313009472 0.742 0.75 7.38E−96 Sod1  3.76E−100 −0.238388169 0.998 0.983 9.33E−96 Man2a1  3.97E−100 0.369999358 0.83 0.583 9.87E−96 mt-Nd6  5.56E−100 −0.515107457 0.389 0.577 1.38E−95 Hint2  6.90E−100 −0.299309844 0.685 0.676 1.71E−95 Map3k5  9.44E−100 0.21643947 0.411 0.147 2.34E−95 Ndufb6 1.29E−99 −0.311202811 0.77 0.759 3.20E−95 Palmd 2.20E−99 0.284673594 0.51 0.219 5.47E−95 Eef2 2.45E−99 0.289562847 0.979 0.873 6.07E−95 Vtn 7.94E−99 0.225160672 0.999 0.983 1.97E−94 Mgll 8.46E−99 0.321840174 0.739 0.449 2.10E−94 Aff4 2.96E−98 0.344186222 0.635 0.337 7.35E−94 Aidh1l1 5.72E−98 0.277372649 0.991 0.904 1.42E−93 Wdr45b 7.36E−98 0.246836045 0.459 0.181 1.83E−93 Gpd2 4.41E−97 0.23284812 0.393 0.135 1.10E−92 Atp2a2 5.61E−97 0.350363266 0.771 0.495 1.39E−92 Gadd45a 2.31E−96 0.231268974 0.41 0.149 5.73E−92 Mbnl2 3.16E−96 0.249293642 0.444 0.172 7.84E−92 Eif1a 3.45E−96 0.295219945 0.583 0.289 8.58E−92 Igf1 4.40E−96 0.277138761 0.989 0.904 1.09E−91 Acaa1b 4.51E−96 −0.263859024 0.968 0.969 1.12E−91 Slc30a5 6.46E−96 0.207315427 0.378 0.126 1.60E−91 Cyb5r3 1.19E−95 0.337684684 0.906 0.725 2.97E−91 Il13ra1 1.45E−95 0.214635625 0.402 0.143 3.59E−91 Slc3a1 8.64E−95 0.290117272 0.464 0.189 2.15E−90 Serpina1e 1.78E−94 0.233787997 1 0.999 4.43E−90 Nop58 2.05E−94 0.257566653 0.428 0.162 5.09E−90 Gm2a 2.88E−94 0.341145926 0.704 0.427 7.15E−90 Mvd 3.47E−94 −0.327327327 0.085 0.269 8.62E−90 Por 5.01E−94 0.290745567 0.898 0.675 1.24E−89 Sparcl1 7.09E−94 −0.253616986 0 0.136 1.76E−89 Rpl13a 2.36E−93 −0.314606263 0.858 0.868 5.86E−89 Enpp2 4.99E−93 0.316882991 0.635 0.345 1.24E−88 Mpc2 5.01E−93 −0.268047152 0.887 0.857 1.24E−88 Ambp 1.48E−92 0.211238054 0.999 0.993 3.68E−88 Cyp1a2 2.74E−92 −0.481919967 0.685 0.794 6.81E−88 Dstn 2.99E−92 0.271381717 0.664 0.37 7.43E−88 Sec14l4 1.89E−91 0.285169227 0.724 0.436 4.69E−87 Slc38a3 3.88E−91 0.292400046 0.971 0.858 9.64E−87 Xdh 1.64E−90 0.27224472 0.541 0.258 4.07E−86 Cfhr2 2.18E−90 −0.246923339 0.949 0.868 5.42E−86 Slc16a6 3.73E−90 0.21530975 0.251 0.054 9.27E−86 Spin1 4.09E−90 0.232119983 0.478 0.206 1.02E−85 Dusp1 1.05E−89 0.300628481 0.539 0.259 2.62E−85 Ubc 1.64E−89 −0.273242853 0.907 0.872 4.07E−85 Aadac 2.86E−89 −0.230855362 0.952 0.86 7.10E−85 Txnrd1 3.72E−89 0.314979852 0.721 0.441 9.23E−85 Serinc3 1.70E−88 0.293964974 0.713 0.433 4.23E−84 Dbi 2.25E−88 0.243173797 0.999 0.971 5.58E−84 C8a 4.69E−88 0.294064237 0.978 0.887 1.16E−83 Eci2 1.71E−87 0.288159513 0.896 0.698 4.24E−83 Chd1 1.87E−87 0.213257509 0.42 0.166 4.65E−83 Elovl2 2.58E−87 0.285038606 0.912 0.699 6.42E−83 Atf6 2.81E−87 0.280521162 0.553 0.273 6.99E−83 Lrp6 3.24E−87 0.270740438 0.505 0.232 8.05E−83 Sigmar1 3.24E−86 −0.282364617 0.482 0.514 8.06E−82 Myo18a 4.13E−86 0.233717966 0.476 0.211 1.03E−81 Gck 6.71E−86 0.260705425 0.557 0.278 1.67E−81 Creg1 7.37E−86 −0.235698597 0.966 0.926 1.83E−81 Atp5f1 1.54E−85 −0.217555876 0.943 0.869 3.81E−81 Ndufa6 1.99E−85 −0.25272382 0.846 0.798 4.93E−81 Id3 2.15E−85 0.399520373 0.688 0.426 5.34E−81 Asl 3.26E−85 0.297673772 0.934 0.787 8.09E−81 Tgm2 7.71E−85 0.316575272 0.524 0.258 1.91E−80 Cpb2 8.35E−85 0.280302458 0.959 0.813 2.07E−80 Uroc1 2.12E−84 0.329587334 0.837 0.615 5.26E−80 Aox3 2.49E−84 0.275388909 0.989 0.894 6.17E−80 Ddi2 3.40E−84 0.302519699 0.642 0.365 8.45E−80 Flnb 1.82E−83 0.212710481 0.376 0.139 4.52E−79 Arl4d 2.11E−83 −0.328520283 0.326 0.437 5.23E−79 Fgf1 2.25E−83 0.287983029 0.647 0.369 5.60E−79 H6pd 1.67E−82 0.300492669 0.825 0.595 4.14E−78 Ctsb 5.86E−82 0.268200419 0.943 0.781 1.46E−77 Ddx5 6.19E−82 0.251675045 0.778 0.515 1.54E−77 Megf9 6.32E−82 0.211011671 0.401 0.158 1.57E−77 Mttp 7.25E−82 0.296651415 0.888 0.697 1.80E−77 Il6st 7.72E−82 0.262348153 0.544 0.273 1.92E−77 Gm9843 1.32E−81 −0.343302667 0.197 0.299 3.27E−77 Gde1 2.63E−81 0.222485647 0.531 0.263 6.54E−77 Trp53inp1 4.94E−81 0.269278401 0.582 0.308 1.23E−76 Rmnd5a 6.65E−81 0.273473023 0.628 0.352 1.65E−76 Fads1 7.07E−81 0.267264464 0.889 0.663 1.76E−76 Gm10250 8.47E−81 −0.30688429 0.124 0.251 2.10E−76 Nrp1 1.23E−80 0.268796793 0.518 0.253 3.05E−76 Rbm47 1.71E−80 0.21054927 0.475 0.218 4.24E−76 Lrp1 1.77E−80 0.310226628 0.831 0.591 4.39E−76 C4bp 2.36E−80 0.26668764 0.948 0.788 5.86E−76 Prox1 2.55E−80 0.31520499 0.622 0.351 6.34E−76 Cebpa 2.62E−80 −0.260692112 0.688 0.672 6.50E−76 Angptl4 3.50E−80 0.315315425 0.838 0.629 8.70E−76 Lbp 9.96E−80 0.264248666 0.605 0.333 2.47E−75 Hs6st1 1.18E−79 0.206647988 0.524 0.261 2.94E−75 Dcxr 1.24E−79 −0.271339616 0.629 0.631 3.07E−75 Zfp683 1.36E−79 −0.421689112 0 0.116 3.38E−75 Clu 1.37E−79 0.2220984 0.995 0.958 3.40E−75 Cox7b 1.54E−79 −0.304638563 0.91 0.878 3.82E−75 Picalm 1.72E−79 0.276902165 0.648 0.376 4.27E−75 Acly 1.84E−79 0.287663867 0.715 0.445 4.57E−75 Malat1 2.78E−79 −0.652623643 0.704 0.78 6.90E−75 Elovl3 4.42E−79 −0.25229278 0.838 0.827 1.10E−74 Atp5h 9.55E−79 −0.351854327 0.688 0.682 2.37E−74 Hs3st3b1 1.01E−78 0.242350838 0.501 0.241 2.50E−74 Ppp2r5a 3.76E−78 −0.263513608 0.593 0.594 9.33E−74 Azin1 4.10E−78 0.268891169 0.59 0.322 1.02E−73 Tmed5 5.21E−78 0.296018777 0.74 0.492 1.29E−73 Tbl1xr1 8.70E−78 0.204315292 0.418 0.176 2.16E−73 Hist1h1c 1.16E−77 −0.331045753 0.24 0.372 2.88E−73 Copa 1.43E−77 0.251410027 0.633 0.363 3.55E−73 Gnl3 4.69E−77 0.242175469 0.454 0.204 1.16E−72 Bhmt 5.22E−77 −0.236483408 0.988 0.956 1.30E−72 Sord 8.74E−77 −0.228716308 0.964 0.931 2.17E−72 Pik3c2a 2.22E−76 0.232920912 0.444 0.198 5.51E−72 Sec14l2 3.93E−76 −0.220330298 0.905 0.856 9.77E−72 Smoc1 7.72E−76 0.212439914 0.49 0.238 1.92E−71 Hipk3 1.02E−75 0.225614187 0.472 0.223 2.53E−71 Hhex 1.26E−75 −0.283483187 0.229 0.307 3.12E−71 Ppib 1.31E−75 −0.223880669 0.823 0.767 3.26E−71 Ctsl 1.52E−75 0.256520866 0.976 0.857 3.77E−71 Iqgap2 2.67E−75 0.283192936 0.879 0.677 6.63E−71 Acsl4 3.34E−75 0.250793464 0.588 0.323 8.30E−71 Ddc 5.23E−75 −0.216024433 0.475 0.46 1.30E−70 Sc4mol 1.02E−74 −0.23053256 0.669 0.642 2.54E−70 Slc38a4 1.12E−74 0.244607846 0.976 0.877 2.78E−70 Lrpprc 1.15E−74 0.257016288 0.662 0.398 2.84E−70 Lurap1l 1.62E−74 0.241965054 0.563 0.301 4.03E−70 Cyp2c70 3.14E−74 0.25600888 0.971 0.834 7.79E−70 Hsd3b3 5.05E−74 −0.226222481 0.631 0.605 1.26E−69 Gstm3 1.28E−73 −0.470077922 0.343 0.414 3.17E−69 Ass1 1.92E−73 0.216965784 0.996 0.962 4.76E−69 Cfi 2.17E−73 0.226479679 0.988 0.905 5.38E−69 Ppp1r3b 5.81E−73 0.259418401 0.642 0.38 1.44E−68 Arhgef12 7.47E−73 0.280147378 0.667 0.408 1.85E−68 Usp9x 1.10E−72 0.233121474 0.556 0.299 2.72E−68 Ranbp2 1.47E−72 0.208744477 0.596 0.338 3.64E−68 Fbp1 1.75E−72 0.236214341 0.997 0.938 4.33E−68 Ndufc2 1.98E−72 −0.202304309 0.639 0.579 4.91E−68 Nr2f6 2.24E−72 −0.219631094 0.417 0.434 5.57E−68 Ywhag 6.54E−72 0.215838932 0.563 0.308 1.62E−67 Dpy19l1 7.13E−72 0.23352829 0.531 0.277 1.77E−67 Srpr 7.66E−72 0.223990237 0.647 0.387 1.90E−67 Cmah 7.79E−72 0.247781083 0.721 0.465 1.93E−67 Atp5j 2.01E−71 −0.234964444 0.782 0.757 5.00E−67 Atp1a1 2.96E−71 0.261718912 0.709 0.457 7.36E−67 Cyp2c55 5.49E−71 −0.316565473 0.103 0.243 1.36E−66 Calr 5.63E−71 0.232562138 0.972 0.885 1.40E−66 Fdx1 9.23E−71 −0.213846254 0.669 0.625 2.29E−66 Gls2 1.99E−70 0.296143664 0.868 0.657 4.94E−66 Alas1 2.15E−70 0.283195713 0.905 0.729 5.33E−66 Ftl1 2.87E−70 −0.346327339 0.394 0.409 7.14E−66 Pklr 3.63E−70 0.25984035 0.624 0.368 9.00E−66 Hsd17b13 6.39E−70 0.351593878 0.907 0.74 1.59E−65 Pnpla7 6.61E−70 0.251226201 0.807 0.572 1.64E−65 Tprkb 1.03E−69 −0.254084951 0.508 0.528 2.56E−65 Osbpl1a 1.14E−69 0.247696779 0.721 0.473 2.84E−65 Comt 1.83E−69 0.220396792 0.99 0.931 4.54E−65 Nucks1 2.40E−69 0.249253158 0.683 0.43 5.96E−65 Pim3 2.64E−69 0.280137371 0.764 0.537 6.55E−65 Cldn1 3.97E−69 −0.246774022 0.21 0.306 9.86E−65 Nek7 4.17E−69 0.204786835 0.517 0.271 1.03E−64 P4hb 5.11E−69 0.204526132 0.995 0.941 1.27E−64 Tm9sf2 5.15E−69 0.208759009 0.616 0.362 1.28E−64 Akr1c20 6.04E−69 −0.230255116 0.563 0.564 1.50E−64 Ldha 6.21E−69 0.234882634 0.974 0.896 1.54E−64 Mtus1 1.13E−68 0.268076242 0.674 0.42 2.80E−64 Me1 1.63E−68 0.229105587 0.699 0.447 4.06E−64 Ptplad1 1.74E−68 0.255273084 0.741 0.496 4.33E−64 Cnbp 6.67E−68 −0.203726646 0.828 0.778 1.66E−63 Prdx4 9.03E−68 −0.205807709 0.653 0.607 2.24E−63 Cyp4a12a 1.79E−67 0.259776426 0.823 0.597 4.43E−63 Hdlbp 2.95E−67 0.267317937 0.894 0.713 7.33E−63 Dhrs3 6.96E−67 −0.21828148 0.451 0.465 1.73E−62 Nedd4 1.42E−66 0.259978699 0.762 0.524 3.52E−62 Rpl14 2.56E−66 −0.261157069 0.559 0.574 6.35E−62 Mafb 2.56E−66 0.216162055 0.577 0.33 6.36E−62 Aplp2 3.47E−66 0.234842456 0.844 0.625 8.61E−62 Kif21a 1.13E−65 0.240302185 0.537 0.293 2.82E−61 Macf1 1.69E−65 0.203727526 0.447 0.219 4.19E−61 Myo1b 2.38E−65 0.247482254 0.776 0.542 5.91E−61 Uba1 3.31E−65 0.23027391 0.662 0.416 8.22E−61 Kmo 9.11E−65 0.262269388 0.891 0.732 2.26E−60 Copz1 9.86E−65 0.221023165 0.631 0.385 2.45E−60 Slc2a2 1.09E−64 0.218249447 0.722 0.479 2.70E−60 Efna1 2.10E−64 0.256152989 0.551 0.309 5.22E−60 Lpin2 2.47E−64 0.232988713 0.817 0.597 6.13E−60 Ak3 2.57E−64 0.224559231 0.893 0.7 6.38E−60 Agpat6 3.96E−64 0.242639639 0.749 0.517 9.83E−60 Rcl1 1.06E−63 0.273905375 0.734 0.514 2.63E−59 Ndufb4 1.26E−63 −0.233018121 0.486 0.49 3.13E−59 Zfp36l1 7.83E−63 0.271823824 0.636 0.402 1.95E−58 D4Wsu53e 3.61E−62 −0.201263472 0.393 0.385 8.97E−58 Wdr26 1.03E−61 0.207089713 0.646 0.406 2.55E−57 Nr1i3 1.86E−61 −0.317940692 0.294 0.377 4.63E−57 Coa6 2.21E−61 −0.242879305 0.344 0.373 5.49E−57 Mup1 2.62E−61 −0.490972296 0.609 0.583 6.50E−57 Vkorc1 3.89E−61 −0.206999378 0.545 0.54 9.65E−57 Minos1 7.23E−61 −0.201913176 0.638 0.595 1.80E−56 Mir692-1 9.07E−61 −0.20556011 0.012 0.126 2.25E−56 Dusp6 9.26E−61 0.205655249 0.491 0.261 2.30E−56 Slco1b2 1.29E−60 −0.207101647 0.976 0.951 3.21E−56 Cldn3 4.13E−60 −0.24877302 0.273 0.355 1.02E−55 Csde1 4.27E−60 0.209918785 0.797 0.577 1.06E−55 Cyp3a59 1.17E−59 −0.263118105 0.281 0.344 2.91E−55 Mpc1 1.33E−59 −0.205050162 0.349 0.369 3.31E−55 4931406C07Rik 1.39E−59 −0.233221778 0.789 0.748 3.45E−55 Eif4g1 7.29E−59 0.201528669 0.865 0.669 1.81E−54 Rab1 8.62E−59 0.211939923 0.673 0.438 2.14E−54 Cyp3a16 9.45E−59 −0.229013809 0.05 0.17 2.35E−54 Dio1 5.55E−58 −0.238782365 0.544 0.542 1.38E−53 Cltc 7.51E−58 0.238358233 0.647 0.414 1.86E−53 Mrps18c 8.71E−58 −0.211258064 0.403 0.394 2.16E−53 Dpyd 1.40E−57 0.207189814 0.857 0.659 3.48E−53 Reep3 2.41E−57 0.201856133 0.654 0.422 5.99E−53 Hsdl2 2.60E−57 0.206098727 0.669 0.438 6.46E−53 Gas5 2.71E−57 −0.204205779 0.552 0.527 6.72E−53 Tmem19 3.39E−57 0.214785487 0.693 0.465 8.41E−53 Rps15 4.18E−57 −0.213338023 0.581 0.528 1.04E−52 Ogdh 6.23E−57 0.220189108 0.601 0.37 1.55E−52 Nr0b2 1.12E−56 −0.203060823 0.227 0.28 2.79E−52 Itih1 2.96E−56 0.213777239 0.946 0.816 7.34E−52 Mcl1 3.89E−56 0.206406082 0.601 0.371 9.67E−52 Pank1 1.20E−55 0.222539616 0.873 0.704 2.97E−51 Phlda1 2.67E−55 0.201287476 0.583 0.356 6.63E−51 0610005C13Rik 7.80E−55 −0.2011928 0.677 0.653 1.94E−50 Idh1 8.52E−55 0.208112098 0.921 0.766 2.12E−50 8430408G22Rik 1.10E−54 −0.221336883 0.336 0.392 2.73E−50 Gdf15 3.32E−54 0.246982665 0.595 0.37 8.25E−50 Gpd1 4.44E−54 0.200332863 0.856 0.665 1.10E−49 Brd2 4.86E−54 0.258446853 0.629 0.408 1.21E−49 Mup14 6.29E−54 −0.340890047 0.699 0.616 1.56E−49 Hc 3.01E−53 0.223732951 0.976 0.903 7.48E−49 Atp5j2 3.31E−53 −0.218750887 0.887 0.852 8.22E−49 Adh6-ps1 4.46E−53 −0.22400228 0.259 0.313 1.11E−48 Ubb 8.42E−53 −0.263773933 0.448 0.45 2.09E−48 Dap 1.08E−52 0.20987441 0.842 0.654 2.68E−48 Gm24245 1.08E−52 −0.254157233 0.192 0.214 2.68E−48 Gstm1 4.17E−52 −0.221666006 0.984 0.935 1.03E−47 Atp5d 5.05E−52 0.209976794 0.871 0.712 1.25E−47 Ssr3 1.09E−51 0.214262703 0.796 0.596 2.71E−47 Sdc1 1.41E−51 0.202649914 0.686 0.469 3.51E−47 Pxmp4 1.72E−51 0.233212684 0.731 0.526 4.27E−47 Blvrb 2.50E−50 −0.243251643 0.562 0.564 6.20E−46 Rps18 2.68E−50 −0.269206741 0.584 0.578 6.67E−46 Fabp2 3.16E−50 −0.226921259 0.631 0.622 7.84E−46 Chchd2 4.37E−48 −0.200916511 0.953 0.916 1.09E−43 Cyp2f2 4.96E−48 0.275177176 0.965 0.863 1.23E−43 F5 1.38E−47 0.202197412 0.886 0.728 3.44E−43 Cyp2e1 2.57E−47 −0.301497571 0.817 0.911 6.38E−43 Rabac1 4.21E−47 −0.211715679 0.522 0.524 1.05E−42 Timm13 2.26E−46 −0.204422177 0.695 0.671 5.61E−42 Tsc22d1 1.34E−45 −0.235196773 0.158 0.242 3.32E−41 Cyp3a44 8.16E−45 −0.205800676 0.164 0.183 2.03E−40 Rnase4 2.92E−44 0.221993349 0.986 0.921 7.25E−40 Fbxo21 8.37E−44 −0.200640929 0.249 0.298 2.08E−39 Iigp1 9.35E−44 0.232002466 0.895 0.759 2.32E−39 Cyp4a10 1.19E−43 −0.289941035 0.614 0.657 2.96E−39 Gadd45b 8.19E−40 −0.219990566 0.254 0.291 2.03E−35 Ifi27 4.76E−36 0.228184801 0.632 0.453 1.18E−31 Mup20 2.24E−32 −0.244695365 1 1 5.57E−28 Lect2 1.65E−31 −0.274252442 0.297 0.414 4.10E−27 Saa3 8.72E−29 0.298054041 0.195 0.087 2.17E−24 Oat 5.39E−28 −0.255537891 0.502 0.611 1.34E−23 Csad 9.84E−28 0.204004276 0.872 0.744 2.44E−23 Mup7 0.007896043 −0.293978105 0.998 0.998 1

TABLE 5c Differentially expressed genes between time point PHX3 FC.15 and untreated (UT). p_val avg_logFC pct.1 pct.2 p_val_adj Saa2 0 2.971862499 0.999 0.222 0 Mt1 0 2.610854994 1 0.556 0 Mt2 0 2.6060431 1 0.365 0 Saa1 0 2.202156726 1 0.662 0 Steap4 0 1.890015167 0.973 0.222 0 Serpina3n 0 1.759758939 0.992 0.574 0 Lcn2 0 1.499141183 0.815 0.07 0 Lpin1 0 1.327657625 0.94 0.31 0 n-R5-8s1 0 1.289598504 0.805 0.031 0 Igfbp1 0 1.288789902 0.99 0.717 0 Cxcl1 0 1.230398019 0.919 0.314 0 Scd1 0 1.081676999 0.998 0.901 0 Gm26924 0 1.063463323 1 1 0 Il1r1 0 0.998168131 0.8 0.167 0 Fga 0 0.981249724 1 0.997 0 Gm24601 0 0.924568273 0.661 0.015 0 Nnmt 0 0.901052904 0.97 0.716 0 Itih4 0 0.887186241 0.999 0.948 0 St3gal5 0 0.882761517 0.915 0.49 0 Tacc2 0 0.877623973 0.707 0.071 0 Lrg1 0 0.870250525 0.981 0.736 0 Fam134b 0 0.865578177 0.876 0.405 0 Tat 0 0.857965136 0.998 0.903 0 Saa4 0 0.854921603 0.981 0.749 0 Thrsp 0 0.836598219 0.98 0.627 0 Slc39a14 0 0.831584936 0.849 0.343 0 Lars2 0 0.816795688 1 0.994 0 Fgg 0 0.809322713 1 0.991 0 Slc38a2 0 0.797899442 0.874 0.413 0 Serpina3m 0 0.779052745 0.961 0.722 0 Hp 0 0.774785279 1 0.999 0 Fgb 0 0.739519125 1 1 0 Gm15564 0 0.735157137 0.999 0.956 0 Serpina10 0 0.733655099 0.934 0.641 0 Plin2 0 0.720463076 0.952 0.714 0 Aass 0 0.705615345 0.965 0.716 0 Fmo5 0 0.690160801 0.991 0.837 0 Fn1 0 0.684266092 0.983 0.821 0 Fkbp5 0 0.663304836 0.665 0.117 0 Slc25a47 0 0.635928777 0.994 0.927 0 Mat1a 0 0.623734998 0.999 0.966 0 Aldob 0 0.490200848 1 0.996 0 Mup3 0 −0.526410044 1 1 0 Cyb5 0 −0.71965743 0.992 0.983 0 mt-Rnr1 0 −0.872186844 1 1 0 mt-Rnr2 0 −0.873557854 1 1 0 Mup11 0 −0.976755523 0.996 1 0 mt-Nd2 0 −1.128776891 0.996 0.999 0 mt-Nd1 0 −1.136736863 0.999 1 0 mt-Nd5 0 −1.145550707 0.974 0.995 0 mt-Co3 0 −1.233961828 0.106 0.603 0 Gm13775 0 −1.255657303 0.205 0.761 0 mt-Cytb 0 −1.296043506 0.993 0.999 0 mt-Co2 0 −1.341686736 0.1 0.629 0 mt-Co1 0 −1.381307687 0.986 0.999 0 mt-Nd4 0 −1.630375247 0.977 0.998 0 Mup4 0 −1.805301681 0.374 0.898 0 Mup6 0 −2.386597202 0.714 0.992 0 Mup9 0 −2.453596744 0.401 0.976 0 Mup17 0 −2.514472885 0.899 1 0 Mup18 0 −2.617739049 0.547 0.997 0 Mup19 0 −2.932276479 0.84 1 0 Acox1 1.48219693752374e−323 0.540022158 0.998 0.966 3.68059143525895e−319 Hnf4a  7.4109846876187e−323 0.644195253 0.969 0.743 1.84029571762948e−318 B3galt1  1.9812032398234e−321 0.788734938 0.634 0.163 4.91972388512946e−317 Cyp2b10 2.53603896010312e−320 −1.254972098 0.132 0.542 6.29749194572806e−316 Mup5  4.3570167109802e−319 −1.484560547 0.52 0.839  1.0819343896706e−314 H3f3b 9.60962621817683e−319 0.755567107 0.831 0.419 2.38626238249767e−314 Btg2 8.06389468707594e−310 0.772686832 0.708 0.241  2.00E−305 Sephs2  8.7749437218295e−310 0.618707003 0.974 0.761  2.18E−305 Ankrd55  1.57E−296 −1.464696038 0.374 0.696  3.90E−292 Hspb8  1.87E−295 0.667847253 0.914 0.597  4.63E−291 Slc7a2  5.58E−288 0.622326529 0.964 0.735  1.38E−283 Cldn14  9.96E−284 0.511583526 0.505 0.076  2.47E−279 C3  5.41E−282 0.482674202 0.999 0.99  1.34E−277 Gjb2  7.14E−278 0.639507436 0.901 0.572  1.77E−273 Rcan1  1.17E−277 0.509239866 0.522 0.085  2.90E−273 Errfi1  8.92E−268 0.500850526 0.998 0.911  2.21E−263 Pfkfb3  1.02E−265 0.426580733 0.421 0.039  2.53E−261 Arhgef26  1.60E−264 0.568544702 0.67 0.203  3.96E−260 Cyp2c29  3.59E−262 −1.027267705 0.751 0.93  8.92E−258 Egfr  9.60E−255 0.555834247 0.989 0.809  2.39E−250 Gsta3  1.42E−250 −0.53784222 0.993 0.956  3.53E−246 Bcl3  1.69E−248 0.419650143 0.479 0.074  4.19E−244 Snx10  3.34E−247 0.558244633 0.63 0.188  8.29E−243 Pck1  8.81E−247 0.43447474 0.999 0.987  2.19E−242 Mup16  3.38E−246 −0.848726713 0.816 0.934  8.40E−242 Bach1  1.06E−243 0.533237374 0.589 0.151  2.63E−239 Tifa  8.54E−243 0.392339477 0.393 0.036  2.12E−238 Hpx  9.49E−242 0.460272423 1 0.997  2.36E−237 Ugt2b5  8.09E−241 −0.423085187 0.991 0.959  2.01E−236 Etnk2  2.61E−240 0.592353201 0.918 0.655  6.47E−236 2010003K11Rik  8.39E−239 0.372219971 0.412 0.046  2.08E−234 Rapgef4  8.83E−238 0.588317735 0.836 0.436  2.19E−233 Tiparp  5.11E−233 0.489122153 0.485 0.087  1.27E−228 Gpt2  3.36E−230 0.533331785 0.949 0.725  8.35E−226 Slc25a25  7.55E−227 0.544465891 0.945 0.704  1.87E−222 Mup10  7.12E−224 0.428268029 0.965 0.692  1.77E−219 Txnip  3.44E−223 0.552612237 0.741 0.297  8.55E−219 Cyp2c50  1.01E−219 −0.763912176 0.693 0.888  2.51E−215 Xbp1  2.95E−219 0.539986 0.89 0.57  7.32E−215 Upp2  5.05E−218 0.541753512 0.934 0.673  1.25E−213 Mfsd2a  1.53E−217 0.496351884 0.563 0.148  3.79E−213 Ephb3  3.99E−217 0.188403248 0.244 0.001  9.91E−213 Actb  2.09E−216 0.456981443 0.99 0.886  5.19E−212 mmu-mir-6236  7.20E−215 0.468866739 0.989 0.837  1.79E−210 Fbf1  1.39E−212 0.298573909 0.336 0.027  3.44E−208 Hsd3b5  2.37E−209 −0.587528886 0.49 0.587  5.88E−205 Trib1  2.88E−209 0.581754281 0.705 0.308  7.14E−205 Arg1  5.85E−205 0.381616351 1 0.982  1.45E−200 Plin5  2.84E−204 0.489257529 0.736 0.315  7.05E−200 Plk3  4.75E−204 0.488016367 0.644 0.226  1.18E−199 Mup13  1.41E−203 −0.755608269 0.303 0.546  3.49E−199 Mtss1  6.23E−203 0.552137981 0.812 0.454  1.55E−198 Klf6  1.09E−202 0.3616937 0.346 0.034  2.71E−198 Itih3  7.66E−202 0.469631651 0.988 0.89  1.90E−197 Gm23935  3.35E−201 0.498066925 0.999 0.925  8.33E−197 Mup21  2.63E−199 −0.668770594 0.829 0.929  6.54E−195 Adck3  7.31E−199 −0.482940158 0.729 0.764  1.81E−194 Cyp2c54  4.33E−198 −0.712859584 0.491 0.759  1.08E−193 Serpina3c  2.44E−196 −0.554657351 0.118 0.385  6.07E−192 Slc10a2  2.81E−196 0.30563824 0.376 0.05  6.99E−192 Egr1  3.87E−196 0.620480469 0.79 0.447  9.61E−192 Sdc4  3.89E−196 0.43560504 0.986 0.867  9.65E−192 Apcs  4.78E−195 0.573439593 0.854 0.525  1.19E−190 Atf3  8.99E−194 0.597274889 0.56 0.179  2.23E−189 Hsd3b7  1.65E−191 −0.451728474 0.795 0.798  4.11E−187 Orm1  3.32E−190 0.463411533 0.993 0.952  8.25E−186 Pzp  7.87E−190 0.387351113 0.999 0.986  1.95E−185 Glul  9.26E−190 0.478908893 0.58 0.18  2.30E−185 Prg4  6.96E−189 0.480504574 0.585 0.188  1.73E−184 Fgl1  1.60E−188 0.49338252 0.961 0.784  3.96E−184 Gpcpd1  3.68E−188 0.53780646 0.778 0.398  9.13E−184 Klf10  4.93E−188 0.304779554 0.388 0.06  1.22E−183 Rgs16  2.29E−187 0.438105488 0.482 0.113  5.69E−183 Ptp4a1  3.26E−187 0.393137367 0.528 0.145  8.09E−183 mt-Atp6  3.25E−186 −0.852555757 0.138 0.452  8.08E−182 Fam35a  2.34E−184 0.470461753 0.642 0.246  5.82E−180 Rhob  2.95E−184 0.37207281 0.4 0.069  7.32E−180 Mup15  7.32E−184 −1.074409915 0.357 0.617  1.82E−179 Cyp3a25  9.18E−184 −0.41051207 0.928 0.919  2.28E−179 Got1  2.20E−183 0.542891511 0.866 0.587  5.45E−179 Ces1d  8.21E−180 −0.385155368 0.944 0.923  2.04E−175 Shb  1.13E−178 0.430613558 0.589 0.204  2.80E−174 Sds  5.46E−177 0.787094904 0.868 0.67  1.36E−172 Abca1  4.14E−176 0.50506234 0.756 0.377  1.03E−171 1810055G02Rik  7.48E−174 0.382584093 0.528 0.155  1.86E−169 Stat3  9.83E−173 0.460515229 0.701 0.318  2.44E−168 Akr1c6  3.47E−171 −0.43492211 0.992 0.971  8.62E−167 Apoe  9.56E−171 −0.26209828 1 1  2.37E−166 Igfbp4  4.54E−170 0.387861679 0.986 0.866  1.13E−165 Cdkn1a  2.74E−169 0.449325471 0.572 0.195  6.81E−165 Gfra1  5.93E−169 0.474694426 0.835 0.498  1.47E−164 Gc  1.32E−168 0.233764264 1 0.999  3.29E−164 Nrg4  3.45E−168 0.246089001 0.306 0.034  8.57E−164 Ivns1abp  1.41E−166 0.46254094 0.688 0.315  3.49E−162 Fh1  2.37E−165 0.471428771 0.915 0.648  5.89E−161 Myo1e  9.03E−164 0.399456672 0.551 0.182  2.24E−159 Slc41a2  1.17E−163 0.3685439 0.482 0.134  2.92E−159 Mup8  2.13E−163 −0.793731191 0.111 0.373  5.28E−159 Slc25a51  3.33E−163 0.372157664 0.522 0.161  8.26E−159 Psen2  1.99E−162 −0.419555606 0.749 0.774  4.95E−158 Dak  3.59E−162 0.481947664 0.867 0.563  8.92E−158 Apoc4  3.42E−160 −0.356086407 0.999 0.98  8.50E−156 Arid5a  1.19E−159 0.163384737 0.208 0.005  2.96E−155 Fasn  1.87E−159 0.467168076 0.719 0.345  4.65E−155 Bhlhe40  9.36E−159 0.403249298 0.628 0.251  2.32E−154 Tmem87b  4.56E−156 0.288330587 0.415 0.096  1.13E−151 Ddx3x  1.73E−155 0.47100162 0.823 0.513  4.30E−151 Ttr  2.14E−155 0.248320061 1 1  5.31E−151 Aldh1a1  7.53E−152 −0.40245097 0.984 0.956  1.87E−147 Slc25a22  2.20E−151 0.390931532 0.649 0.282  5.45E−147 Rnf103  8.64E−150 0.438540394 0.701 0.35  2.15E−145 Scara5  1.64E−149 0.221632911 0.324 0.054  4.07E−145 B4galt1  3.67E−147 0.321380868 0.494 0.155  9.10E−143 Hacl1  1.26E−146 −0.332899987 0.842 0.797  3.14E−142 Rnf125  1.44E−146 −0.463320018 0.312 0.493  3.57E−142 Gm26917  1.97E−145 0.46739621 0.523 0.181  4.89E−141 Junb  2.51E−145 0.458500682 0.788 0.47  6.24E−141 Cps1  4.13E−145 0.336429448 0.999 0.971  1.03E−140 Atp1b1  1.93E−144 0.424801231 0.567 0.226  4.80E−140 Glud1  7.16E−144 0.341724783 0.991 0.905  1.78E−139 D10Wsu102e  2.65E−142 0.256022156 0.338 0.063  6.58E−138 Hyou1  3.00E−142 0.431109873 0.731 0.385  7.45E−138 Jmjd1c  3.16E−142 0.39612601 0.516 0.178  7.84E−138 Apoa5  7.36E−142 0.30259839 0.999 0.974  1.83E−137 4933426M11Rik  8.78E−142 0.28624304 0.419 0.109  2.18E−137 Scp2  4.38E−141 0.279911381 0.997 0.986  1.09E−136 Jun  2.16E−140 0.479246114 0.864 0.593  5.36E−136 Mup12  3.83E−140 −0.589618573 0.792 0.86  9.51E−136 Cyp2a5  4.16E−140 −0.938183249 0.278 0.555  1.03E−135 Cpt1a  7.83E−140 0.42860734 0.894 0.651  1.94E−135 Pik3r1  1.29E−139 0.389193614 0.577 0.231  3.21E−135 Apob  4.48E−139 0.416824707 0.997 0.989  1.11E−134 Hmox1  1.22E−137 0.169723562 0.22 0.016  3.03E−133 Epas1  1.71E−136 0.38425941 0.646 0.297  4.25E−132 Ugt2b36  7.63E−136 −0.287193139 0.978 0.93  1.90E−131 Mbd1  2.07E−135 0.348094524 0.507 0.176  5.15E−131 Mup2  6.51E−135 −0.650107006 0.161 0.392  1.62E−130 Pik3ap1  9.38E−135 0.19440062 0.283 0.043  2.33E−130 Foxq1  5.32E−134 0.22551931 0.377 0.096  1.32E−129 Slc22a5  7.77E−134 0.185456618 0.32 0.065  1.93E−129 Gadd45g  2.21E−133 0.392031882 0.899 0.639  5.49E−129 Fos  5.81E−133 0.524733327 0.785 0.51  1.44E−128 Bcl2l1  6.28E−133 0.280315334 0.426 0.122  1.56E−128 Ptpn1  8.84E−133 0.268263225 0.402 0.107  2.20E−128 Slc25a15  2.01E−132 0.402049896 0.931 0.738  4.98E−128 Tdo2  6.78E−132 0.25156007 0.999 0.991  1.68E−127 Rnd3  2.06E−131 0.285147682 0.375 0.091  5.12E−127 Adh1  2.79E−131 −0.295980789 0.995 0.96  6.92E−127 Litaf  5.60E−131 0.396007707 0.603 0.278  1.39E−126 Gm5096  6.85E−131 −0.399548106 0.364 0.468  1.70E−126 Wbp1l  8.48E−130 0.409138156 0.867 0.606  2.11E−125 Grn  5.01E−129 0.403315761 0.726 0.396  1.24E−124 Tns1  5.99E−129 0.33981795 0.524 0.196  1.49E−124 Cyp2c37  7.22E−129 −0.662335734 0.314 0.608  1.79E−124 Ahcy  1.24E−128 −0.375627724 0.918 0.916  3.07E−124 Foxa3  4.50E−128 0.307992015 0.505 0.182  1.12E−123 Qsox1  6.27E−128 0.378486857 0.925 0.707  1.56E−123 Cth  9.41E−128 −0.308847665 0.898 0.838  2.34E−123 Id2  2.73E−127 0.430147785 0.826 0.579  6.79E−123 1700017B05Rik  6.88E−127 0.182766029 0.263 0.037  1.71E−122 Myh9  9.03E−127 0.399128031 0.653 0.318  2.24E−122 Cox6c  5.60E−126 −0.41128283 0.893 0.884  1.39E−121 Raph1  2.99E−125 0.242670968 0.382 0.1  7.42E−121 Ier2  4.77E−123 0.452598264 0.763 0.49  1.18E−118 Cfh  5.82E−123 0.312615767 0.991 0.897  1.44E−118 Itih2  1.49E−122 0.336714211 0.984 0.884  3.70E−118 Rsp14  1.37E−121 −0.346340977 0.936 0.917  3.39E−117 Ccnl1  1.51E−121 0.341338448 0.526 0.206  3.76E−117 Cyp8b1  1.66E−121 −0.364571013 0.714 0.745  4.13E−117 Cox4i1  1.99E−121 −0.288035158 0.992 0.958  4.94E−117 Eef1a1  5.92E−121 0.340768186 0.967 0.85  1.47E−116 Nedd4l  2.66E−120 0.271827098 0.447 0.147  6.59E−116 Inmt  6.09E−120 −0.308364158 0.966 0.884  1.51E−115 Cep85l  1.56E−119 0.202664771 0.347 0.089  3.89E−115 Elovl5  6.36E−119 0.382267188 0.863 0.58  1.58E−114 Zbtb16  7.15E−119 0.232600907 0.414 0.131  1.77E−114 Il17ra  2.90E−118 0.203529938 0.302 0.061  7.21E−114 Hip1r  3.46E−118 0.213858215 0.362 0.098  8.58E−114 Plg  4.59E−118 0.26619661 0.998 0.961  1.14E−113 Gcc1  5.36E−118 0.175053461 0.258 0.04  1.33E−113 Eif4g2  7.33E−118 0.384302798 0.905 0.678  1.82E−113 Atg14  1.12E−117 0.231648357 0.369 0.1  2.77E−113 Ppip5k2  1.68E−117 0.30299148 0.51 0.197  4.16E−113 Ulk1  3.53E−117 0.297841785 0.499 0.189  8.77E−113 Pon1  1.13E−116 −0.302819466 0.936 0.906  2.81E−112 Elovl6  1.25E−116 0.37962641 0.553 0.24  3.10E−112 Il6ra  6.00E−116 0.251696836 0.431 0.142  1.49E−111 Adamts1  3.81E−115 0.15752777 0.202 0.018  9.45E−111 Ndufb11  5.66E−115 −0.36792318 0.722 0.735  1.40E−110 Ets2  9.44E−114 0.183062901 0.285 0.056  2.34E−109 Igfbp2  3.42E−113 −0.348403589 0.886 0.885  8.50E−109 Fads2  1.76E−112 0.323744791 0.592 0.273  4.38E−108 Tnfrsf1a  2.66E−112 0.346845029 0.551 0.244  6.61E−108 Gcnt2  3.52E−112 0.221618104 0.333 0.082  8.73E−108 Ugt2b34  3.85E−112 −0.290735843 0.918 0.874  9.57E−108 Ell2  5.46E−112 0.371745977 0.72 0.416  1.36E−107 Ly6e  5.67E−112 0.42022985 0.68 0.386  1.41E−107 Rps2  1.37E−110 −0.44250848 0.675 0.757  3.40E−106 Epb4.1  3.33E−110 0.349430673 0.617 0.304  8.26E−106 Dscr3  6.45E−110 0.180232898 0.339 0.09  1.60E−105 Ptpn2  1.68E−109 0.225408583 0.354 0.097  4.16E−105 Clpx  7.87E−109 −0.306093278 0.818 0.783  1.95E−104 Zc3h13  8.62E−109 0.204542393 0.325 0.083  2.14E−104 Rps27l  4.06E−108 −0.361138678 0.855 0.849  1.01E−103 Dst  5.39E−108 0.329905553 0.507 0.206  1.34E−103 Atl2  1.07E−107 0.321873809 0.674 0.361  2.67E−103 Gm4076  1.67E−107 −0.342157966 0.007 0.184  4.16E−103 Lpgat1  2.80E−107 0.390146943 0.776 0.502  6.94E−103 Gm20594  2.89E−107 −0.559577825 0.108 0.294  7.17E−103 Hmgcs1  6.61E−107 −0.258009688 0.778 0.703  1.64E−102 Esd  1.82E−106 −0.302906103 0.794 0.784  4.52E−102 Oaz1  2.34E−106 −0.339004868 0.759 0.75  5.80E−102 Pptc7  8.06E−106 0.227095018 0.412 0.141  2.00E−101 Sult1a1  1.16E−105 0.371023537 0.899 0.707  2.89E−101 Ctif  2.20E−105 0.18604392 0.312 0.078  5.46E−101 Nfil3  2.44E−105 0.338730712 0.617 0.309  6.05E−101 Aqp8  4.48E−105 −0.331182913 0.444 0.505  1.11E−100 Gpx1  4.61E−105 −0.222094695 1 0.999  1.15E−100 Cyp3a11  5.24E−105 −0.251219977 0.999 1  1.30E−100 Socs3  1.50E−104 0.194515821 0.456 0.183  3.73E−100 Cml1  2.50E−104 −0.277339974 0.803 0.757  6.22E−100 Apoa4  2.57E−104 0.609214916 0.604 0.339  6.38E−100 Jak1  3.30E−104 0.362766687 0.648 0.342  8.21E−100 Arid5b  4.81E−104 0.232391653 0.472 0.186 1.19E−99 Rasgef1b  6.74E−104 0.174426927 0.279 0.06 1.67E−99 Baiap2l1  8.59E−104 0.187103281 0.395 0.136 2.13E−99 Rrs1  1.28E−103 0.167967739 0.314 0.082 3.18E−99 Ralgapa2  2.35E−103 0.20791298 0.334 0.092 5.82E−99 G6pc  4.54E−103 0.341403933 0.948 0.752 1.13E−98 Rlf  6.60E−103 0.176204022 0.321 0.086 1.64E−98 Ifitm3  2.12E−102 0.331673739 0.958 0.812 5.27E−98 Zfp36  2.37E−102 0.407014847 0.776 0.522 5.90E−98 Oaf  5.88E−102 −0.333766768 0.79 0.794 1.46E−97 Mgst1  6.37E−102 −0.322742924 1 0.997 1.58E−97 Uqcrq  9.98E−102 −0.316451873 0.98 0.951 2.48E−97 Garem  4.50E−101 0.204881738 0.351 0.104 1.12E−96 B2m  5.10E−101 0.246889569 0.997 0.963 1.27E−96 Hebp1  3.43E−100 −0.313009472 0.742 0.75 8.51E−96 Man2al  4.10E−100 0.369999358 0.83 0.583 1.02E−95 Sod1  4.17E−100 −0.238388169 0.998 0.983 1.04E−95 mt-Nd6  5.99E−100 −0.515107457 0.389 0.577 1.49E−95 Hint2  8.14E−100 −0.299309844 0.685 0.676 2.02E−95 Map3k5  9.57E−100 0.21643947 0.411 0.147 2.38E−95 Ndufb6 1.46E−99 −0.311202811 0.77 0.759 3.63E−95 Palmd 2.20E−99 0.284673594 0.51 0.219 5.47E−95 Eef2 2.59E−99 0.289562847 0.979 0.873 6.43E−95 3110043O21Rik 3.51E−99 0.171966272 0.282 0.065 8.72E−95 Heatr1 4.14E−99 0.163145002 0.275 0.062 1.03E−94 Mgll 8.58E−99 0.321840174 0.739 0.449 2.13E−94 Vtn 8.69E−99 0.225160672 0.999 0.983 2.16E−94 Aff4 2.98E−98 0.344186222 0.635 0.337 7.41E−94 Aldh1l1 6.03E−98 0.277372649 0.991 0.904 1.50E−93 Wdr45b 7.37E−98 0.246836045 0.459 0.181 1.83E−93 Kdm4a 1.44E−97 0.172058145 0.3 0.077 3.57E−93 Gpd2 4.44E−97 0.23284812 0.393 0.135 1.10E−92 Atp2a2 5.73E−97 0.350363266 0.771 0.495 1.42E−92 Gadd45a 2.33E−96 0.231268974 0.41 0.149 5.79E−92 Mbnl2 3.16E−96 0.249293642 0.444 0.172 7.86E−92 Eif1a 3.47E−96 0.295219945 0.583 0.289 8.63E−92 Igf1 4.62E−96 0.277138761 0.989 0.904 1.15E−91 Acaa1b 4.81E−96 −0.263859024 0.968 0.969 1.20E−91 Slc30a5 6.51E−96 0.207315427 0.378 0.126 1.62E−91 Cyb5r3 1.26E−95 0.337684684 0.906 0.725 3.12E−91 Il13ral 1.46E−95 0.214635625 0.402 0.143 3.62E−91 Dopey2 3.25E−95 0.19521799 0.33 0.097 8.06E−91 Slc3a1 8.66E−95 0.290117272 0.464 0.189 2.15E−90 Serpina1e 1.97E−94 0.233787997 1 0.999 4.90E−90 Nop58 2.05E−94 0.257566653 0.428 0.162 5.10E−90 Gm2a 2.97E−94 0.341145926 0.704 0.427 7.38E−90 Ell 3.83E−94 0.161665745 0.291 0.076 9.52E−90 Mvd 4.11E−94 −0.327327327 0.085 0.269 1.02E−89 Por 5.09E−94 0.290745567 0.898 0.675 1.26E−89 Sparcl1 7.09E−94 −0.253616986 0 0.136 1.76E−89 Rpl13a 2.58E−93 −0.314606263 0.858 0.868 6.42E−89 Enpp2 5.04E−93 0.316882991 0.635 0.345 1.25E−88 Kng1 5.14E−93 0.194558698 1 0.991 1.28E−88 Mpc2 5.50E−93 −0.268047152 0.887 0.857 1.36E−88 Cep110 7.61E−93 0.192096419 0.362 0.121 1.89E−88 Creb3l2 1.57E−92 0.161215013 0.278 0.068 3.90E−88 Ambp 1.66E−92 0.211238054 0.999 0.993 4.13E−88 Cyp1a2 2.87E−92 −0.481919967 0.685 0.794 7.13E−88 Dstn 2.99E−92 0.271381717 0.664 0.37 7.43E−88 Ahsg 1.27E−91 0.171853168 1 1 3.15E−87 Pfkfb2 1.64E−91 0.160198891 0.27 0.067 4.08E−87 Sec14l4 1.90E−91 0.285169227 0.724 0.436 4.71E−87 Slc38a3 4.07E−91 0.292400046 0.971 0.858 1.01E−86 Xdh 1.64E−90 0.27224472 0.541 0.258 4.07E−86 Cfhr2 2.31E−90 −0.246923339 0.949 0.868 5.75E−86 Slc16a6 3.74E−90 0.21530975 0.251 0.054 9.29E−86 Spin1 4.10E−90 0.232119983 0.478 0.206 1.02E−85 Coq10b 5.98E−90 0.153862213 0.313 0.093 1.48E−85 Dusp1 1.06E−89 0.300628481 0.539 0.259 2.64E−85 Ubc 1.78E−89 −0.273242853 0.907 0.872 4.42E−85 Aadac 3.01E−89 −0.230855362 0.952 0.86 7.48E−85 Txnrd1 3.75E−89 0.314979852 0.721 0.441 9.32E−85 Serinc3 1.72E−88 0.293964974 0.713 0.433 4.27E−84 Dbi 2.41E−88 0.243173797 0.999 0.971 5.98E−84 C8a 4.89E−88 0.294064237 0.978 0.887 1.22E−83 Eci2 1.76E−87 0.288159513 0.896 0.698 4.36E−83 Chd1 1.89E−87 0.213257509 0.42 0.166 4.68E−83 Elovl2 2.62E−87 0.285038606 0.912 0.699 6.50E−83 Atf6 2.81E−87 0.280521162 0.553 0.273 6.99E−83 Lrp6 3.24E−87 0.270740438 0.505 0.232 8.05E−83 Sigmar1 4.00E−86 −0.282364617 0.482 0.514 9.94E−82 Myo18a 4.15E−86 0.233717966 0.476 0.211 1.03E−81 Gck 6.71E−86 0.260705425 0.557 0.278 1.67E−81 D5Ertd579e 7.69E−86 0.197825601 0.328 0.104 1.91E−81 Creg1 7.90E−86 −0.235698597 0.966 0.926 1.96E−81 Atp5f1 1.64E−85 −0.217555876 0.943 0.869 4.08E−81 Zfp445 1.92E−85 0.159662672 0.371 0.138 4.77E−81 Ndufa6 2.18E−85 −0.25272382 0.846 0.798 5.42E−81 Id3 2.19E−85 0.399520373 0.688 0.426 5.45E−81 Nfkbiz 2.84E−85 0.157772695 0.249 0.059 7.06E−81 Asl 3.40E−85 0.297673772 0.934 0.787 8.43E−81 Tgm2 7.84E−85 0.316575272 0.524 0.258 1.95E−80 Cpb2 8.61E−85 0.280302458 0.959 0.813 2.14E−80 Uroc1 2.18E−84 0.329587334 0.837 0.615 5.42E−80 Aox3 2.55E−84 0.275388909 0.989 0.894 6.34E−80 Ddi2 3.43E−84 0.302519699 0.642 0.365 8.51E−80 Flnb 1.83E−83 0.212710481 0.376 0.139 4.55E−79 Fgf1 2.26E−83 0.287983029 0.647 0.369 5.61E−79 Arl4d 2.64E−83 −0.328520283 0.326 0.437 6.55E−79 Cobll1 3.37E−83 0.158603105 0.353 0.13 8.38E−79 H6pd 1.71E−82 0.300492669 0.825 0.595 4.25E−78 Tsc22d2 1.99E−82 0.165988347 0.349 0.124 4.94E−78 Ctsb 6.03E−82 0.268200419 0.943 0.781 1.50E−77 Ddx5 6.22E−82 0.251675045 0.778 0.515 1.54E−77 Megf9 6.35E−82 0.211011671 0.401 0.158 1.58E−77 Mttp 7.49E−82 0.296651415 0.888 0.697 1.86E−77 Il6st 7.72E−82 0.262348153 0.544 0.273 1.92E−77 Gm9843 1.66E−81 −0.343302667 0.197 0.299 4.13E−77 Gde1 2.64E−81 0.222485647 0.531 0.263 6.55E−77 Slc35g1 3.46E−81 0.166162728 0.36 0.133 8.58E−77 Trp53inp1 4.94E−81 0.269278401 0.582 0.308 1.23E−76 Rmnd5a 6.65E−81 0.273473023 0.628 0.352 1.65E−76 Fads1 7.11E−81 0.267264464 0.889 0.663 1.77E−76 Gm10250 1.09E−80 −0.30688429 0.124 0.251 2.72E−76 Nrp1 1.23E−80 0.268796793 0.518 0.253 3.05E−76 Rbm47 1.71E−80 0.21054927 0.475 0.218 4.25E−76 Lrp1 1.78E−80 0.310226628 0.831 0.591 4.43E−76 C4bp 2.42E−80 0.26668764 0.948 0.788 6.01E−76 Prox1 2.57E−80 0.31520499 0.622 0.351 6.37E−76 Cebpa 2.97E−80 −0.260692112 0.688 0.672 7.37E−76 Angptl4 3.62E−80 0.315315425 0.838 0.629 8.99E−76 Clip1 4.55E−80 0.166877376 0.438 0.196 1.13E−75 Cish 6.12E−80 0.172549219 0.302 0.093 1.52E−75 Lbp 9.99E−80 0.264248666 0.605 0.333 2.48E−75 Hs6st1 1.19E−79 0.206647988 0.524 0.261 2.96E−75 Zfp683 1.36E−79 −0.421689112 0 0.116 3.38E−75 Dcxr 1.42E−79 −0.271339616 0.629 0.631 3.54E−75 Clu 1.46E−79 0.2220984 0.995 0.958 3.62E−75 Cox7b 1.64E−79 −0.304638563 0.91 0.878 4.07E−75 Picalm 1.73E−79 0.276902165 0.648 0.376 4.29E−75 Acly 1.84E−79 0.287663867 0.715 0.445 4.57E−75 Malat1 2.85E−79 −0.652623643 0.704 0.78 7.08E−75 Elovl3 4.71E−79 −0.25229278 0.838 0.827 1.17E−74 Hs3st3b1 1.01E−78 0.242350838 0.501 0.241 2.50E−74 Atp5h 1.05E−78 −0.351854327 0.688 0.682 2.61E−74 Nit2 2.04E−78 −0.196867848 0.62 0.577 5.06E−74 Ipo7 2.49E−78 0.176153152 0.402 0.168 6.18E−74 Uox 3.63E−78 0.189986074 0.998 0.965 9.02E−74 Azin1 4.11E−78 0.268891169 0.59 0.322 1.02E−73 Ppp2r5a 4.38E−78 −0.263513608 0.593 0.594 1.09E−73 Tmed5 5.30E−78 0.296018777 0.74 0.492 1.32E−73 Tbl1xr1 8.75E−78 0.204315292 0.418 0.176 2.17E−73 Hist1h1c 1.42E−77 −0.331045753 0.24 0.372 3.53E−73 Copa 1.43E−77 0.251410027 0.633 0.363 3.55E−73 Gnl3 4.69E−77 0.242175469 0.454 0.204 1.16E−72 Bhmt 5.54E−77 −0.236483408 0.988 0.956 1.38E−72 Sord 9.31E−77 −0.228716308 0.964 0.931 2.31E−72 Nr1d2 9.97E−77 0.159943118 0.411 0.179 2.48E−72 Rhobtb1 1.53E−76 0.178172942 0.406 0.172 3.79E−72 Pik3c2a 2.22E−76 0.232920912 0.444 0.198 5.51E−72 Sec14l2 4.24E−76 −0.220330298 0.905 0.856 1.05E−71 Ythdc1 5.44E−76 0.15157378 0.369 0.15 1.35E−71 Smoc1 7.76E−76 0.212439914 0.49 0.238 1.93E−71 Plec 8.16E−76 0.197499812 0.424 0.186 2.03E−71 Hipk3 1.02E−75 0.225614187 0.472 0.223 2.54E−71 Ppib 1.44E−75 −0.223880669 0.823 0.767 3.57E−71 Ctsl 1.56E−75 0.256520866 0.976 0.857 3.88E−71 Bag3 1.58E−75 0.187468684 0.376 0.148 3.92E−71 Hhex 1.66E−75 −0.283483187 0.229 0.307 4.12E−71 Angptl3 1.98E−75 −0.18094369 0.993 0.944 4.92E−71 Iqgap2 2.71E−75 0.283192936 0.879 0.677 6.73E−71 Acsl4 3.34E−75 0.250793464 0.588 0.323 8.30E−71 Nr1i2 4.36E−75 0.198788095 0.505 0.252 1.08E−70 Clp1 5.19E−75 0.153048593 0.307 0.103 1.29E−70 Ddc 6.37E−75 −0.216024433 0.475 0.46 1.58E−70 Lrpprc 1.15E−74 0.257016288 0.662 0.398 2.85E−70 Sc4mol 1.15E−74 −0.23053256 0.669 0.642 2.86E−70 Slc38a4 1.16E−74 0.244607846 0.976 0.877 2.89E−70 Lurap1l 1.62E−74 0.241965054 0.563 0.301 4.03E−70 Akap11 2.01E−74 0.187807202 0.392 0.164 4.99E−70 Cyp2c70 3.18E−74 0.25600888 0.971 0.834 7.90E−70 Gstp1 5.43E−74 0.197542109 0.962 0.822 1.35E−69 Hsd3b3 5.80E−74 −0.226222481 0.631 0.605 1.44E−69 Sec24a 8.91E−74 0.188750112 0.504 0.255 2.21E−69 Sepp1 1.07E−73 0.16148927 1 1 2.66E−69 Gstm3 1.41E−73 −0.470077922 0.343 0.414 3.51E−69 Ass1 2.01E−73 0.216965784 0.996 0.962 5.00E−69 Cfi 2.24E−73 0.226479679 0.988 0.905 5.56E−69 Ppp1r3b 5.81E−73 0.259418401 0.642 0.38 1.44E−68 Arhgef12 7.49E−73 0.280147378 0.667 0.408 1.86E−68 Usp9x 1.10E−72 0.233121474 0.556 0.299 2.72E−68 Ranbp2 1.47E−72 0.208744477 0.596 0.338 3.65E−68 Fbp1 1.80E−72 0.236214341 0.997 0.938 4.47E−68 Ndufc2 2.25E−72 −0.202304309 0.639 0.579 5.59E−68 Trip11 2.44E−72 0.163424021 0.429 0.2 6.05E−68 Nr2f6 2.86E−72 −0.219631094 0.417 0.434 7.10E−68 2900026A02Rik 4.55E−72 0.175166554 0.416 0.187 1.13E−67 Rc3h1 4.74E−72 0.165519544 0.33 0.122 1.18E−67 Ywhag 6.56E−72 0.215838932 0.563 0.308 1.63E−67 Dpy19l1 7.13E−72 0.23352829 0.531 0.277 1.77E−67 Srpr 7.66E−72 0.223990237 0.647 0.387 1.90E−67 Cmah 7.79E−72 0.247781083 0.721 0.465 1.93E−67 Ssfa2 8.16E−72 0.162814615 0.354 0.141 2.03E−67 Apoc3 1.24E−71 0.187850611 0.999 0.993 3.08E−67 Atp5j 2.23E−71 −0.234964444 0.782 0.757 5.53E−67 Atp1a1 2.98E−71 0.261718912 0.709 0.457 7.40E−67 Ppp1r15a 5.29E−71 0.157408911 0.336 0.13 1.31E−66 Calr 5.87E−71 0.232562138 0.972 0.885 1.46E−66 Cyp2c55 6.60E−71 −0.316565473 0.103 0.243 1.64E−66 Fdx1 1.04E−70 −0.213846254 0.669 0.625 2.58E−66 Gls2 2.00E−70 0.296143664 0.868 0.657 4.98E−66 Alas1 2.18E−70 0.283195713 0.905 0.729 5.42E−66 Cdip1 3.17E−70 0.161158186 0.514 0.273 7.88E−66 Ftl1 3.30E−70 −0.346327339 0.394 0.409 8.20E−66 Pklr 3.63E−70 0.25984035 0.624 0.368 9.02E−66 Tmem205 4.55E−70 −0.196745573 0.978 0.934 1.13E−65 Hsd17b13 6.48E−70 0.351593878 0.907 0.74 1.61E−65 Pnpla7 6.64E−70 0.251226201 0.807 0.572 1.65E−65 Ech1 9.17E−70 −0.191877671 0.908 0.856 2.28E−65 Osbpl1a 1.15E−69 0.247696779 0.721 0.473 2.86E−65 Tprkb 1.21E−69 −0.254084951 0.508 0.528 3.01E−65 Arl8b 1.47E−69 0.198760529 0.468 0.228 3.65E−65 Comt 1.92E−69 0.220396792 0.99 0.931 4.76E−65 Nucks1 2.40E−69 0.249253158 0.683 0.43 5.97E−65 Pim3 2.68E−69 0.280137371 0.764 0.537 6.66E−65 Nek7 4.18E−69 0.204786835 0.517 0.271 1.04E−64 Tm9sf2 5.16E−69 0.208759009 0.616 0.362 1.28E−64 Cldn1 5.28E−69 −0.246774022 0.21 0.306 1.31E−64 P4hb 5.34E−69 0.204526132 0.995 0.941 1.33E−64 Ldha 6.49E−69 0.234882634 0.974 0.896 1.61E−64 Akr1c20 6.92E−69 −0.230255116 0.563 0.564 1.72E−64 Ripk1 7.80E−69 0.174862366 0.407 0.183 1.94E−64 Ibtk 1.11E−68 0.188149661 0.485 0.247 2.76E−64 Mtus1 1.13E−68 0.268076242 0.674 0.42 2.80E−64 Rdh7 1.26E−68 −0.197994968 0.993 0.969 3.13E−64 Me1 1.64E−68 0.229105587 0.699 0.447 4.06E−64 Ptplad1 1.75E−68 0.255273084 0.741 0.496 4.35E−64 Scarb2 6.47E−68 0.19345963 0.603 0.353 1.61E−63 Cnbp 7.25E−68 −0.203726646 0.828 0.778 1.80E−63 Hagh 9.52E−68 −0.157822564 0.933 0.858 2.36E−63 Prdx4 1.02E−67 −0.205807709 0.653 0.607 2.52E−63 Cep85 1.30E−67 0.171686021 0.383 0.167 3.22E−63 Cyp4a12a 1.79E−67 0.259776426 0.823 0.597 4.45E−63 Hdlbp 3.00E−67 0.267317937 0.894 0.713 7.44E−63 St3gal1 4.24E−67 0.192410856 0.454 0.221 1.05E−62 Gpc4 4.64E−67 0.16318479 0.349 0.141 1.15E−62 Dhrs3 8.37E−67 −0.21828148 0.451 0.465 2.08E−62 Nedd4 1.42E−66 0.259978699 0.762 0.524 3.53E−62 Mafb 2.56E−66 0.216162055 0.577 0.33 6.36E−62 Rpl14 2.95E−66 −0.261157069 0.559 0.574 7.34E−62 Aplp2 3.47E−66 0.234842456 0.844 0.625 8.63E−62 Cap1 5.72E−66 0.156999287 0.42 0.202 1.42E−61 Nploc4 6.46E−66 0.164369249 0.436 0.214 1.60E−61 Atl3 7.09E−66 0.191666389 0.506 0.27 1.76E−61 Kif21a 1.13E−65 0.240302185 0.537 0.293 2.82E−61 Cmbl 1.44E−65 −0.198257983 0.724 0.678 3.56E−61 Macf1 1.70E−65 0.203727526 0.447 0.219 4.22E−61 Alas2 2.09E−65 0.17568703 0.586 0.344 5.20E−61 Actr2 2.14E−65 0.170960453 0.638 0.394 5.33E−61 Gsk3b 2.28E−65 0.159364703 0.41 0.193 5.65E−61 Pcm1 2.32E−65 0.153416983 0.343 0.142 5.76E−61 Myo1b 2.39E−65 0.247482254 0.776 0.542 5.93E−61 Ddx21 2.58E−65 0.186649034 0.448 0.22 6.41E−61 Apoa2 2.71E−65 −0.174241915 1 1 6.74E−61 Itpr1 2.94E−65 0.161076343 0.356 0.152 7.30E−61 Uba1 3.32E−65 0.23027391 0.662 0.416 8.23E−61 Rap1b 3.35E−65 0.174034663 0.491 0.258 8.31E−61 Kmo 9.36E−65 0.262269388 0.891 0.732 2.33E−60 Copz1 9.86E−65 0.221023165 0.631 0.385 2.45E−60 Slc2a2 1.09E−64 0.218249447 0.722 0.479 2.70E−60 Plbd2 1.20E−64 0.169456289 0.42 0.199 2.99E−60 Ythdf3 1.72E−64 0.174850983 0.474 0.243 4.28E−60 Efna1 2.10E−64 0.256152989 0.551 0.309 5.23E−60 Lpin2 2.48E−64 0.232988713 0.817 0.597 6.15E−60 Dnttip2 2.57E−64 0.166547988 0.418 0.199 6.37E−60 Ak3 2.58E−64 0.224559231 0.893 0.7 6.42E−60 Supt6 2.61E−64 0.166662973 0.338 0.137 6.48E−60 Wasl 3.52E−64 0.178274463 0.449 0.223 8.75E−60 Cd1d1 3.89E−64 −0.182746213 0.644 0.612 9.67E−60 Gbe1 3.98E−64 0.183485273 0.577 0.338 9.89E−60 Aypat6 3.99E−64 0.242639639 0.749 0.517 9.90E−60 Nme1 4.59E−64 −0.195199734 0.674 0.622 1.14E−59 Snd1 6.72E−64 0.18406298 0.549 0.312 1.67E−59 Rcl1 1.08E−63 0.273905375 0.734 0.514 2.68E−59 Ndufb4 1.48E−63 −0.233018121 0.486 0.49 3.67E−59 Gpam 3.53E−63 0.169852715 0.417 0.199 8.76E−59 Zfp36l1 7.93E−63 0.271823824 0.636 0.402 1.97E−58 Fgd6 2.48E−62 0.16919996 0.348 0.147 6.16E−58 Larp4 2.62E−62 0.156912192 0.396 0.184 6.50E−58 Atp13a3 4.01E−62 0.197384706 0.65 0.41 9.95E−58 D4Wsu53e 4.36E−62 −0.201263472 0.393 0.385 1.08E−57 Fndc3b 5.07E−62 0.151940318 0.276 0.096 1.26E−57 Slc27a2 9.23E−62 0.192264004 0.991 0.949 2.29E−57 Wdr26 1.03E−61 0.207089713 0.646 0.406 2.56E−57 Nrn1 1.22E−61 −0.19828092 0.704 0.675 3.04E−57 Gns 1.29E−61 0.166751532 0.516 0.288 3.20E−57 Pex11a 1.58E−61 0.185588983 0.681 0.441 3.93E−57 Nr1i3 2.15E−61 −0.317940692 0.294 0.377 5.33E−57 Enpep 2.37E−61 0.192022994 0.374 0.166 5.87E−57 Coa6 2.69E−61 −0.242879305 0.344 0.373 6.69E−57 Mup1 2.75E−61 −0.490972296 0.609 0.583 6.84E−57 Lrrc58 3.23E−61 0.196709613 0.597 0.359 8.03E−57 Dync1h1 3.27E−61 0.187521298 0.428 0.21 8.11E−57 Slc16a10 4.35E−61 0.194608601 0.547 0.315 1.08E−56 Vkorc1 4.55E−61 −0.206999378 0.545 0.54 1.13E−56 Selk 6.14E−61 −0.155942939 0.545 0.486 1.53E−56 Sfpq 7.57E−61 0.159417591 0.425 0.211 1.88E−56 Minos1 8.02E−61 −0.201913176 0.638 0.595 1.99E−56 Dusp6 9.26E−61 0.205655249 0.491 0.261 2.30E−56 Mir692-1 9.43E−61 −0.20556011 0.012 0.126 2.34E−56 Slco1b2 1.34E−60 −0.207101647 0.976 0.951 3.32E−56 Hist1h2bc 1.64E−60 −0.197841473 0.811 0.777 4.08E−56 Itch 2.42E−60 0.151077267 0.399 0.195 6.01E−56 Kif5b 3.67E−60 0.150172912 0.53 0.303 9.11E−56 Csde1 4.27E−60 0.209918785 0.797 0.577 1.06E−55 Ptprk 4.67E−60 0.158881882 0.354 0.156 1.16E−55 Cldn3 5.09E−60 −0.24877302 0.273 0.355 1.26E−55 Rab6a 6.65E−60 0.191200862 0.57 0.335 1.65E−55 Tspan4 1.11E−59 0.181956703 0.451 0.23 2.76E−55 Hao1 1.22E−59 0.196088416 0.924 0.758 3.02E−55 Cyp3a59 1.41E−59 −0.263118105 0.281 0.344 3.49E−55 Birc6 1.47E−59 0.164860409 0.502 0.28 3.64E−55 4931406C07Rik 1.48E−59 −0.233221778 0.789 0.748 3.67E−55 Alkbh5 1.49E−59 0.198532353 0.507 0.279 3.69E−55 Mpc1 1.66E−59 −0.205050162 0.349 0.369 4.13E−55 Ccdc25 6.51E−59 0.153512231 0.493 0.271 1.62E−54 Acacb 6.52E−59 0.172458783 0.33 0.137 1.62E−54 Eif4g1 7.31E−59 0.201528669 0.865 0.669 1.82E−54 Rab1 8.62E−59 0.211939923 0.673 0.438 2.14E−54 Cyp3a16 1.09E−58 −0.229013809 0.05 0.17 2.70E−54 Uqcrb 1.79E−58 −0.157541559 0.721 0.641 4.44E−54 Ghr 1.87E−58 0.197884255 0.963 0.833 4.63E−54 Vgll4 1.91E−58 0.152050279 0.363 0.164 4.75E−54 Psmb1 2.41E−58 −0.18427868 0.822 0.759 5.97E−54 Ebpl 2.69E−58 −0.155251391 0.48 0.451 6.68E−54 F11 4.57E−58 0.183078168 0.512 0.287 1.13E−53 Cpne3 5.54E−58 0.182285896 0.537 0.31 1.38E−53 C8g 5.92E−58 −0.1570956 0.965 0.91 1.47E−53 Akr1c19 6.19E−58 −0.179403044 0.547 0.527 1.54E−53 Dio1 6.28E−58 −0.238782365 0.544 0.542 1.56E−53 Cltc 7.51E−58 0.238358233 0.647 0.414 1.87E−53 Cct8 9.58E−58 0.156517607 0.674 0.445 2.38E−53 Mrps18c 1.03E−57 −0.211258064 0.403 0.394 2.55E−53 Dpyd 1.41E−57 0.207189814 0.857 0.659 3.49E−53 Tram1 1.71E−57 0.180903738 0.737 0.512 4.26E−53 Sec31a 2.22E−57 0.151339369 0.53 0.31 5.50E−53 Reep3 2.41E−57 0.201856133 0.654 0.422 5.99E−53 Hsdl2 2.60E−57 0.206098727 0.669 0.438 6.46E−53 Eif4b 3.01E−57 0.163112238 0.666 0.438 7.47E−53 Gas5 3.06E−57 −0.204205779 0.552 0.527 7.60E−53 Tmem19 3.39E−57 0.214785487 0.693 0.465 8.43E−53 Sf3b1 3.86E−57 0.196390125 0.637 0.406 9.58E−53 Gys2 3.98E−57 0.152105722 0.582 0.358 9.87E−53 Rps15 4.60E−57 −0.213338023 0.581 0.528 1.14E−52 Ogdh 6.23E−57 0.220189108 0.601 0.37 1.55E−52 Huwe1 7.01E−57 0.177152033 0.536 0.314 1.74E−52 Slc25a1 8.35E−57 0.187178873 0.724 0.499 2.07E−52 Naa50 9.32E−57 0.187968549 0.586 0.358 2.31E−52 Nab1 1.31E−56 0.151021868 0.533 0.315 3.25E−52 Nr0b2 1.48E−56 −0.203060823 0.227 0.28 3.68E−52 Pah 1.72E−56 0.196282042 0.983 0.891 4.27E−52 Itih1 3.00E−56 0.213777239 0.946 0.816 7.46E−52 Vwa8 3.49E−56 0.184402682 0.534 0.311 8.66E−52 Mcl1 3.89E−56 0.206406082 0.601 0.371 9.67E−52 Acadl 4.71E−56 0.192143091 0.819 0.612 1.17E−51 Trp53inp2 4.88E−56 0.176936721 0.655 0.428 1.21E−51 Chchd1 5.13E−56 −0.178218308 0.469 0.438 1.27E−51 Kpna1 5.35E−56 0.161541953 0.411 0.206 1.33E−51 Ndufa4 6.33E−56 −0.196233158 0.941 0.889 1.57E−51 Rhou 6.93E−56 0.192074068 0.559 0.333 1.72E−51 Pcca 7.47E−56 0.150589178 0.594 0.373 1.85E−51 Arl5a 9.28E−56 0.169926786 0.508 0.289 2.30E−51 Clcn4-2 1.08E−55 0.160606741 0.492 0.276 2.68E−51 Pank1 1.21E−55 0.222539616 0.873 0.704 3.01E−51 Phlda1 2.67E−55 0.201287476 0.583 0.356 6.63E−51 Ugt1a1 2.89E−55 0.183517826 0.502 0.283 7.18E−51 Amfr 2.93E−55 0.184512887 0.738 0.516 7.27E−51 Nars 2.97E−55 0.191856779 0.696 0.471 7.38E−51 Hspa4 4.00E−55 0.171672026 0.728 0.506 9.93E−51 Arf4 5.56E−55 0.159979368 0.58 0.36 1.38E−50 0610005C13Rik 8.56E−55 −0.2011928 0.677 0.653 2.13E−50 Idh1 8.60E−55 0.208112098 0.921 0.766 2.13E−50 Furin 9.57E−55 0.191384876 0.643 0.417 2.38E−50 Atp5a1 1.01E−54 0.174138529 0.984 0.895 2.50E−50 Ddx17 1.12E−54 0.159893824 0.491 0.277 2.79E−50 8430408G22Rik 1.33E−54 −0.221336883 0.336 0.392 3.30E−50 St3gal4 1.39E−54 0.159434184 0.456 0.244 3.44E−50 Ndufb8 1.42E−54 −0.158878768 0.79 0.746 3.53E−50 Etf1 1.44E−54 0.198764917 0.636 0.409 3.58E−50 Gdf15 3.33E−54 0.246982665 0.595 0.37 8.26E−50 Gpd1 4.45E−54 0.200332863 0.856 0.665 1.11E−49 Tlcd2 4.61E−54 −0.168255558 0.563 0.536 1.14E−49 Brd2 4.88E−54 0.258446853 0.629 0.408 1.21E−49 Mup14 6.56E−54 −0.340890047 0.699 0.616 1.63E−49 Hc 3.08E−53 0.223732951 0.976 0.903 7.65E−49 Atp5j2 3.49E−53 −0.218750887 0.887 0.852 8.66E−49 Ifitm2 3.98E−53 0.199025687 0.568 0.347 9.88E−49 Adh6-ps1 5.41E−53 −0.22400228 0.259 0.313 1.34E−48 Cp 6.17E−53 0.17916098 0.993 0.943 1.53E−48 Slc30a10 8.57E−53 0.166623301 0.442 0.238 2.13E−48 Aars 8.79E−53 0.199299553 0.699 0.479 2.18E−48 Ubb 9.48E−53 −0.263773933 0.448 0.45 2.35E−48 Dap 1.08E−52 0.20987441 0.842 0.654 2.69E−48 Gm24245 1.31E−52 −0.254157233 0.192 0.214 3.25E−48 Rpl35 1.57E−52 −0.175144379 0.216 0.225 3.91E−48 Ireb2 1.70E−52 0.163596475 0.536 0.321 4.21E−48 Ugdh 1.95E−52 0.175644914 0.808 0.604 4.84E−48 Ywhab 2.03E−52 0.186791118 0.656 0.434 5.04E−48 Hgfac 2.16E−52 0.181878452 0.66 0.438 5.37E−48 Prdx1 2.84E−52 −0.174743472 0.971 0.927 7.05E−48 Capzb 3.07E−52 0.162969545 0.561 0.344 7.63E−48 Akr1c14 3.37E−52 −0.173913844 0.758 0.707 8.37E−48 Pdcd6ip 3.67E−52 0.181372134 0.556 0.338 9.12E−48 Sppl2a 4.25E−52 0.169493485 0.769 0.56 1.05E−47 Gstm1 4.25E−52 −0.221666006 0.984 0.935 1.06E−47 Atp5d 5.14E−52 0.209976794 0.871 0.712 1.28E−47 Man1a 5.65E−52 0.190591338 0.799 0.595 1.40E−47 Arcn1 6.44E−52 0.158407448 0.582 0.366 1.60E−47 Narf 6.90E−52 0.163638744 0.46 0.253 1.71E−47 Ssr3 1.09E−51 0.214262703 0.796 0.596 2.72E−47 Ubr4 1.10E−51 0.17740179 0.455 0.25 2.74E−47 Fam195a 1.24E−51 −0.190271304 0.355 0.373 3.08E−47 Ifrd1 1.27E−51 0.175156039 0.379 0.185 3.15E−47 Sdc1 1.41E−51 0.202649914 0.686 0.469 3.51E−47 Mrp63 1.68E−51 −0.184375029 0.563 0.531 4.18E−47 Pxmp4 1.74E−51 0.233212684 0.731 0.526 4.32E−47 Nlrp12 1.79E−51 0.153172692 0.648 0.43 4.44E−47 1110008F13Rik 2.27E−51 −0.197564988 0.666 0.648 5.64E−47 Uqcr11 3.71E−51 −0.196760374 0.918 0.879 9.21E−47 Gna12 4.75E−51 −0.191090072 0.352 0.354 1.18E−46 Gm4952 4.76E−51 −0.180740052 0.551 0.533 1.18E−46 Cat 5.57E−51 0.151152692 0.998 0.971 1.38E−46 Ppm1k 6.46E−51 −0.198117939 0.469 0.45 1.60E−46 Hint1 7.66E−51 −0.15108001 0.915 0.858 1.90E−46 Slc35d1 1.45E−50 0.1666456 0.651 0.435 3.61E−46 Sult1d1 1.50E−50 −0.183796178 0.739 0.684 3.72E−46 Bzw1 1.97E−50 0.162308789 0.558 0.344 4.89E−46 Ces1e 2.56E−50 0.166391723 0.779 0.576 6.36E−46 Blvrb 2.69E−50 −0.243251643 0.562 0.564 6.69E−46 Rps18 2.90E−50 −0.269206741 0.584 0.578 7.20E−46 Abca6 3.37E−50 0.198869605 0.719 0.507 8.36E−46 Fabp2 3.39E−50 −0.226921259 0.631 0.622 8.42E−46 Apol7a 3.48E−50 −0.165242629 0.39 0.382 8.65E−46 Nudt4 3.71E−50 0.183172596 0.773 0.568 9.21E−46 Grlf1 4.39E−50 0.163008664 0.457 0.257 1.09E−45 Son 5.47E−50 0.188921988 0.573 0.358 1.36E−45 Lgals9 5.77E−50 0.184003378 0.936 0.793 1.43E−45 Rtfdc1 7.57E−50 0.16242752 0.627 0.412 1.88E−45 Serbp1 1.02E−49 0.186271124 0.824 0.634 2.54E−45 Pqlc1 1.31E−49 −0.161639859 0.364 0.36 3.26E−45 Osbpl9 1.67E−49 0.161985999 0.661 0.448 4.15E−45 Ttc36 1.68E−49 −0.175280872 0.983 0.95 4.17E−45 Zbtb20 3.03E−49 0.197963292 0.657 0.445 7.53E−45 Eprs 3.05E−49 0.19400896 0.7 0.488 7.57E−45 A1cf 3.11E−49 0.163393145 0.66 0.449 7.72E−45 Agt 5.44E−49 0.169771558 0.941 0.817 1.35E−44 Ubr2 6.83E−49 0.158348096 0.464 0.265 1.70E−44 Lrrc59 6.85E−49 0.163232541 0.484 0.28 1.70E−44 Aco2 9.03E−49 0.155048742 0.702 0.493 2.24E−44 Pten 1.24E−48 0.166403783 0.669 0.458 3.07E−44 Cbs 1.25E−48 0.199528185 0.901 0.749 3.10E−44 Dhcr24 1.81E−48 0.165813919 0.932 0.783 4.49E−44 Pygl 2.29E−48 0.19507544 0.92 0.776 5.68E−44 Prkar1a 2.52E−48 0.165756705 0.67 0.46 6.26E−44 Commd6 2.96E−48 −0.168923514 0.391 0.39 7.36E−44 Chchd2 4.53E−48 −0.200916511 0.953 0.916 1.13E−43 Cyp2f2 4.99E−48 0.275177176 0.965 0.863 1.24E−43 Glol 5.98E−48 −0.154642914 0.804 0.749 1.49E−43 Dnajc19 6.41E−48 −0.156899631 0.412 0.387 1.59E−43 Atxn7l3b 7.88E−48 0.191387966 0.686 0.476 1.96E−43 Col18a1 9.42E−48 0.159648412 0.934 0.79 2.34E−43 Rpl36a1 1.01E−47 −0.186625637 0.601 0.551 2.51E−43 F5 1.39E−47 0.202197412 0.886 0.728 3.45E−43 Ppp2ca 1.60E−47 0.154757155 0.64 0.43 3.98E−43 Paics 1.64E−47 0.198478345 0.842 0.662 4.08E−43 Gsta2 1.74E−47 −0.188661153 0.296 0.333 4.33E−43 Psma4 1.83E−47 −0.153086391 0.544 0.495 4.55E−43 Dnaja2 1.91E−47 0.160071794 0.612 0.402 4.75E−43 Cyp2e1 2.58E−47 −0.301497571 0.817 0.911 6.41E−43 Nadk 3.79E−47 0.15446959 0.661 0.454 9.40E−43 Rabac1 4.67E−47 −0.211715679 0.522 0.524 1.16E−42 Slc31a1 8.37E−47 0.182041621 0.693 0.486 2.08E−42 Sco2 8.41E−47 −0.198692618 0.507 0.508 2.09E−42 Mrpl41 1.76E−46 −0.172436199 0.341 0.348 4.38E−42 Gnas 1.80E−46 0.159624116 0.947 0.82 4.47E−42 AI182371 2.26E−46 0.179018804 0.81 0.622 5.61E−42 Timm13 2.42E−46 −0.204422177 0.695 0.671 6.02E−42 Gchfr 3.03E−46 −0.152643272 0.833 0.768 7.51E−42 Gyk 3.44E−46 0.150378816 0.553 0.35 8.55E−42 Etnk1 4.88E−46 0.15045907 0.527 0.328 1.21E−41 Ndufs6 6.02E−46 −0.195648216 0.771 0.724 1.49E−41 9430023L20Rik 7.56E−46 −0.164422856 0.264 0.282 1.88E−41 Map1lc3b 1.57E−45 0.167697241 0.602 0.395 3.89E−41 Tsc22d1 1.58E−45 −0.235196773 0.158 0.242 3.92E−41 Clmn 2.09E−45 0.159639031 0.509 0.31 5.20E−41 Hdac11 2.63E−45 −0.196507741 0.251 0.285 6.53E−41 Edem1 2.95E−45 0.172255296 0.635 0.429 7.32E−41 Fah 3.84E−45 0.188483379 0.941 0.834 9.54E−41 Gstt3 5.49E−45 −0.159722425 0.296 0.286 1.36E−40 Pbld1 5.50E−45 −0.1818338 0.592 0.565 1.37E−40 Gstm4 6.47E−45 −0.157553603 0.478 0.444 1.61E−40 Crp 6.68E−45 0.178468102 0.905 0.756 1.66E−40 Tgoln1 7.76E−45 0.176355766 0.768 0.575 1.93E−40 Rps19 9.26E−45 −0.151004347 0.562 0.474 2.30E−40 Neat1 9.39E−45 0.164921803 0.293 0.135 2.33E−40 Anp32a 9.68E−45 −0.154984115 0.436 0.413 2.40E−40 Ndufb2 1.00E−44 −0.154329774 0.685 0.629 2.49E−40 Cyp3a44 1.00E−44 −0.205800676 0.164 0.183 2.49E−40 Ndufa2 1.04E−44 −0.194549142 0.792 0.738 2.57E−40 1110058L19Rik 1.49E−44 −0.160260673 0.272 0.281 3.69E−40 Surf4 1.87E−44 0.150111361 0.746 0.551 4.64E−40 Hspa9 2.74E−44 0.158702904 0.947 0.824 6.81E−40 Sdha 2.84E−44 0.152056738 0.902 0.747 7.06E−40 Rnase4 2.95E−44 0.221993349 0.986 0.921 7.33E−40 Trip12 3.21E−44 0.158568104 0.544 0.345 7.98E−40 Acadsb 3.48E−44 0.161705277 0.79 0.601 8.65E−40 Qprt 5.28E−44 0.156064415 0.698 0.498 1.31E−39 Afm 7.47E−44 0.159606308 0.745 0.55 1.86E−39 Iigp1 9.44E−44 0.232002466 0.895 0.759 2.34E−39 Fbxo21 9.92E−44 −0.200640929 0.249 0.298 2.46E−39 Cyp4a10 1.24E−43 −0.289941035 0.614 0.657 3.08E−39 Hrsp12 1.65E−43 −0.156961195 0.98 0.939 4.11E−39 H2-D1 1.76E−43 0.167536811 0.916 0.774 4.38E−39 Slc22a1 2.39E−43 −0.199196167 0.777 0.747 5.94E−39 Bche 2.46E−43 0.162843566 0.566 0.369 6.11E−39 Skp1a 2.87E−43 0.172529381 0.791 0.606 7.13E−39 Tspo 4.64E−43 −0.171115456 0.532 0.506 1.15E−38 Pgrmc1 5.46E−43 0.159063843 0.99 0.94 1.36E−38 Cyp2c44 9.90E−43 0.164710905 0.863 0.698 2.46E−38 1810022K09Rik 1.34E−42 −0.180096346 0.286 0.301 3.32E−38 Kcnk5 2.83E−42 −0.168374452 0.107 0.173 7.02E−38 Selenbp1 4.91E−42 −0.185040969 0.725 0.699 1.22E−37 Fetub 1.37E−41 0.174405959 0.859 0.703 3.41E−37 Cox8a 2.26E−41 0.176195798 0.796 0.621 5.62E−37 Srp9 2.81E−41 −0.160772329 0.333 0.336 6.97E−37 Serping1 3.58E−41 0.153322882 0.963 0.87 8.90E−37 Gstt2 5.06E−41 −0.190732451 0.397 0.404 1.26E−36 2410015M20Rik 5.10E−41 −0.169256363 0.635 0.604 1.27E−36 Pglyrp2 7.08E−41 0.150653064 0.607 0.414 1.76E−36 Mug2 9.73E−41 0.179746266 0.887 0.738 2.42E−36 Rpl32 1.01E−40 −0.190948597 0.8 0.757 2.51E−36 Tmem106b 3.79E−40 0.153891421 0.743 0.557 9.40E−36 Tomm70a 4.81E−40 0.151256378 0.685 0.494 1.19E−35 Mettl20 4.88E−40 −0.163343248 0.311 0.327 1.21E−35 Gadd45b 9.33E−40 −0.219990566 0.254 0.291 2.32E−35 S100a10 1.12E−39 −0.177702028 0.676 0.662 2.79E−35 Htatip2 1.90E−39 −0.152544453 0.334 0.329 4.73E−35 Hspe1 1.98E−39 −0.157908691 0.6 0.557 4.91E−35 Sqstm1 4.03E−39 0.16784685 0.923 0.805 1.00E−34 Ndufa7 5.40E−39 −0.18650272 0.739 0.718 1.34E−34 Canx 1.10E−38 0.163661783 0.941 0.835 2.74E−34 Gdi2 1.73E−38 0.15496797 0.782 0.605 4.30E−34 Sucnr1 2.03E−38 −0.171877738 0.101 0.201 5.04E−34 1500011K16Rik 7.21E−38 −0.156897838 0.297 0.312 1.79E−33 Slc37a4 1.47E−37 0.154508476 0.687 0.502 3.66E−33 Sfxn1 3.26E−37 0.177292254 0.68 0.496 8.10E−33 Rplp0 2.95E−36 −0.152097782 0.828 0.791 7.32E−32 Rplp1 4.29E−36 −0.196523046 0.782 0.757 1.06E−31 Ifi27 4.78E−36 0.228184801 0.632 0.453 1.19E−31 Hsd17b12 1.08E−35 0.150192807 0.811 0.647 2.69E−31 Gm11273 1.47E−35 −0.154535944 0.034 0.102 3.66E−31 1100001G20Rik 1.71E−35 −0.181522579 0.998 0.982 4.24E−31 Atf4 1.03E−34 0.170664039 0.622 0.442 2.55E−30 Rps9 1.44E−34 −0.160672445 0.733 0.675 3.57E−30 mt-Ti 1.42E−33 −0.175221151 0.091 0.167 3.52E−29 Etnppl 3.38E−33 0.199542145 0.769 0.606 8.40E−29 Krt18 3.64E−33 0.185376047 0.771 0.617 9.04E−29 Mup20 2.28E−32 −0.244695365 1 1 5.67E−28 Cox5b 2.57E−32 −0.184963493 0.747 0.726 6.38E−28 Wdr89 4.58E−32 −0.157854036 0.08 0.118 1.14E−27 Bcar3 4.86E−32 −0.154603512 0.132 0.193 1.21E−27 Lect2 1.72E−31 −0.274252442 0.297 0.414 4.27E−27 Ddt 1.57E−30 −0.172944365 0.847 0.829 3.91E−26 Saa3 8.77E−29 0.298054041 0.195 0.087 2.18E−24 Oat 5.46E−28 −0.255537891 0.502 0.611 1.36E−23 Csad 9.84E−28 0.204004276 0.872 0.744 2.44E−23 mmu-mir-6240 3.16E−24 −0.197588471 0.054 0.115 7.85E−20 Cyp7a1 2.27E−21 −0.191761184 0.186 0.259 5.64E−17 Gulo 1.13E−20 −0.161523894 0.482 0.497 2.80E−16 Mup7 0.007903215 −0.293978105 0.998 0.998 1

TABLE 6 Differentially Expressed genes between time point PH48 and untreated (UT) p_val avg_logFC pct. 1 pct. 2 p_val_adj Saa2 0 4.43818759 0.995 0.222 0 Saa1 0 3.650785996 0.999 0.662 0 Orm2 0 2.405086745 0.882 0.09 0 Lcn2 0 2.39758181 0.862 0.07 0 Saa3 0 2.199786317 0.629 0.087 0 Apes 0 2.049485412 0.922 0.525 0 Orm1 0 1.823760769 0.997 0.952 0 Hp 0 1.584889895 1 0.999 0 Fgl1 0 1.561880768 0.967 0.784 0 Gm26924 0 1.445355764 1 1 0 Hpx 0 1.443685235 1 0.997 0 Itih4 0 1.171742648 0.99 0.948 0 C3 0 0.982337034 0.998 0.99 0 Apoe 0 −0.615882949 0.999 1 0 Apoa2 0 −0.615981195 0.997 1 0 mt-Nd1 0 −1.154630438 0.967 1 0 mt-Nd2 0 −1.189410874 0.935 0.999 0 Mup20 0 −1.237817166 0.94 1 0 mt-Cytb 0 −1.378313317 0.921 0.999 0 mt-Co1 0 −1.399110403 0.911 0.999 0 Mup11 0 −1.415092329 0.925 1 0 Mup3 0 −1.423759103 0.999 1 0 mt-Nd4 0 −1.673140231 0.851 0.998 0 Mup4 0 −1.945646142 0.168 0.898 0 Mup9 0 −2.219144293 0.238 0.976 0 Mup17 0 −2.2696211 0.683 1 0 Mup18 0 −2.373348742 0.455 0.997 0 Mup6 0 −2.645373468 0.413 0.992 0 Mup19 0 −3.632170505 0.355 1 0 Car3  8.09E−306 −1.292191881 0.738 0.974  2.01E−301 mt-Nd5  5.14E−305 −1.397897502 0.833 0.995  1.28E−300 Itih3  1.63E−301 1.223022315 0.963 0.89  4.04E−297 Mt1  3.98E−297 1.733946488 0.899 0.556  9.88E−293 Mup21  5.31E−295 −1.346645152 0.379 0.929  1.32E−290 n-R5-8s1  1.18E−287 1.223121237 0.464 0.031  2.94E−283 Mup5  8.36E−285 −1.768987649 0.189 0.839  2.08E−280 2810007J24Rik  1.06E−277 −1.093998287 0.598 0.943  2.63E−273 Mt2  8.20E−276 1.558205591 0.812 0.365  2.04E−271 Tdo2  2.59E−271 −0.736504592 0.9 0.991  6.44E−267 Rbp4  5.33E−264 −0.580599925 0.98 0.999  1.32E−259 Ankrd55  1.01E−251 −1.950942364 0.023 0.696  2.52E−247 Fga  3.73E−250 0.968748472 0.992 0.997  9.27E−246 Mup12  4.44E−248 −1.210517374 0.304 0.86  1.10E−243 Lars2  1.90E−226 0.849538102 0.996 0.994  4.73E−222 Gm13775  1.60E−220 −1.145210977 0.163 0.761  3.97E−216 Fabp1  3.30E−218 −0.542167351 0.993 1  8.21E−214 Lrg1  6.20E−218 1.051046086 0.905 0.736  1.54E−213 Hsd11b1  1.59E−213 −0.998666341 0.494 0.875  3.95E−209 mt-Co2  2.22E−213 −1.417328219 0.024 0.629  5.51E−209 Ces3a  5.70E−211 −0.721008165 0.796 0.967  1.41E−206 Hmgcs2  2.42E−210 −0.664269004 0.865 0.986  6.01E−206 Mup15  9.41E−207 −1.364182598 0.022 0.617  2.34E−202 Serpina1d  2.36E−203 −0.586852756 0.896 0.988  5.86E−199 Selenbp2  3.91E−198 −0.857199402 0.581 0.937  9.70E−194 Ugt2b5  5.94E−195 −0.683262994 0.84 0.959  1.47E−190 Hrsp12  6.38E−187 −0.800669662 0.701 0.939  1.58E−182 Fgb  5.69E−184 0.677592366 0.999 1  1.41E−179 Gm24601  1.08E−180 0.675379727 0.292 0.015  2.68E−176 Acaa1b  3.58E−179 −0.742478092 0.668 0.969  8.89E−175 mt-Co3  3.92E−179 −1.212388388 0.066 0.603  9.73E−175 Serpina3n  1.88E−173 1.082720183 0.805 0.574  4.67E−169 Fgg  1.38E−171 0.702140119 0.996 0.991  3.42E−167 Ambp  1.08E−167 0.4774812 0.995 0.993  2.69E−163 Ces3b  2.76E−165 −0.819558687 0.344 0.787  6.86E−161 Cyp2d9  3.51E−155 −0.616676578 0.806 0.959  8.72E−151 Elovl3  7.26E−155 −0.812250701 0.396 0.827  1.80E−150 Mup16  8.52E−154 −0.87654486 0.529 0.934  2.12E−149 Trf  6.44E−153 0.436833817 0.997 1  1.60E−148 Retsat  2.20E−152 −0.784380771 0.457 0.83  5.47E−148 Gm15564  1.74E−150 0.746211054 0.962 0.956  4.32E−146 Ugt2b36  4.45E−150 −0.629671114 0.751 0.93  1.10E−145 Cox4i1  9.84E−146 −0.57523009 0.814 0.958  2.44E−141 mt-Rnr2  1.08E−145 −0.51967923 1 1  2.69E−141 Rnase4  1.72E−145 0.836959148 0.933 0.921  4.28E−141 Prtn3  3.48E−145 0.327267898 0.2 0.003  8.65E−141 Ugt2b1  2.29E−144 −0.722102286 0.573 0.871  5.69E−140 Serpina3k  1.35E−142 −0.279762031 0.999 1  3.34E−138 H2-K1  7.00E−142 −0.596584494 0.803 0.936  1.74E−137 Apoa4  1.21E−141 1.186863065 0.658 0.339  3.01E−137 Cyp2f2  2.11E−140 −0.887034648 0.469 0.863  5.25E−136 Pigr  4.34E−139 −0.661452 0.741 0.947  1.08E−134 Rdh7  2.25E−136 −0.496910675 0.848 0.969  5.58E−132 Hsd3b5  1.44E−133 −0.886463454 0.146 0.587  3.58E−129 Mup13  7.62E−132 −0.870972392 0.107 0.546  1.89E−127 Apoa1  2.09E−131 −0.336207866 1 1  5.20E−127 Apoh  1.60E−130 −0.417935459 0.945 0.986  3.98E−126 Aadac  2.72E−126 −0.747342823 0.623 0.86  6.76E−122 Ephx2  6.00E−126 −0.570800981 0.72 0.937  1.49E−121 Gpx1  9.51E−125 −0.321984135 0.991 0.999  2.36E−120 Gsta3  1.01E−122 −0.579823037 0.89 0.956  2.50E−118 Fam25c  1.11E−122 0.96762143 0.653 0.356  2.76E−118 Alb  1.03E−121 −0.427719117 1 1  2.56E−117 mt-Atp6  1.35E−121 −0.914635453 0.034 0.452  3.35E−117 Otc  6.05E−121 −0.584972427 0.713 0.914  1.50E−116 Cp  5.68E−120 0.620221202 0.952 0.943  1.41E−115 Dhcr24  6.64E−120 0.759730578 0.862 0.783  1.65E−115 Apoa5  1.27E−119 −0.470514722 0.85 0.974  3.16E−115 Mup7  1.06E−118 −0.847726732 0.936 0.998  2.63E−114 Cyb5  5.01E−113 −0.486476838 0.951 0.983  1.24E−108 Serpina10  1.45E−111 0.871044179 0.772 0.641  3.60E−107 Nnmt  1.55E−111 0.768076272 0.825 0.716  3.84E−107 Mug1  1.45E−109 −0.497189268 0.891 0.989  3.61E−105 Slc25a47  1.13E−108 −0.555532536 0.691 0.927  2.81E−104 Acsl1  1.46E−108 −0.568030382 0.652 0.924  3.63E−104 Akr1c6  4.20E−108 −0.501143524 0.901 0.971  1.04E−103 Cfh  1.01E−107 0.588715272 0.911 0.897  2.52E−103 Igfbp2  3.61E−107 −0.576682095 0.605 0.885  8.96E−103 Kng1  1.58E−106 0.419944891 0.979 0.991  3.92E−102 Cyp4v3  5.88E−106 −0.600614165 0.542 0.827  1.46E−101 Slco1a1  2.22E−105 −0.632477905 0.443 0.777  5.52E−101 Csf2ra  1.40E−104 0.342712543 0.158 0.005  3.48E−100 Mup2  8.60E−103 −0.738721984 0.024 0.392 2.14E−98 Cyp4a10  1.05E−102 −0.698160085 0.263 0.657 2.61E−98 Cfhr2  3.06E−102 −0.630617674 0.669 0.868 7.59E−98 B2m  8.51E−102 −0.430851295 0.886 0.963 2.11E−97 mmu-mir-6236  2.21E−101 0.632369146 0.903 0.837 5.49E−97 D17H6S56E-5  8.56E−100 0.560241333 0.152 0.005 2.13E−95 Hsd3b7 2.07E−97 −0.581642142 0.495 0.798 5.15E−93 Mup8 1.52E−95 −0.829956435 0.025 0.373 3.77E−91 Khk 3.58E−95 −0.530150378 0.672 0.863 8.89E−91 Apoc1 4.18E−95 −0.31073779 0.993 0.999 1.04E−90 Cyp8b1 4.37E−95 −0.565483524 0.393 0.745 1.09E−90 C4bp 3.00E−94 0.530516995 0.852 0.788 7.45E−90 Uox 5.71E−94 −0.480422343 0.901 0.965 1.42E−89 Rarres2 7.11E−94 −0.492013911 0.712 0.905 1.76E−89 Serpina12 3.03E−93 −0.612367467 0.122 0.492 7.52E−89 Cxcl14 3.17E−93 0.268462966 0.132 0.002 7.87E−89 Serpina3c 3.47E−93 −0.589926828 0.042 0.385 8.61E−89 Cyp2b10 4.76E−92 −0.995219016 0.209 0.542 1.18E−87 Serpinc1 5.56E−92 −0.333556351 0.966 0.983 1.38E−87 Ugt2a3 9.37E−92 −0.54739922 0.46 0.773 2.33E−87 Serpinf1 1.23E−89 −0.506061854 0.631 0.864 3.06E−85 Hsp90ab1 4.96E−88 0.455851506 0.923 0.922 1.23E−83 Ttr 1.56E−86 −0.286138394 0.998 1 3.87E−82 Adck3 2.56E−86 −0.569692886 0.504 0.764 6.36E−82 Ces1d 9.77E−86 −0.445283361 0.726 0.923 2.43E−81 Tmem176a 1.45E−85 0.675060004 0.637 0.429 3.59E−81 C8g 9.70E−85 −0.455638561 0.751 0.91 2.41E−80 Isyna1 3.42E−84 0.320415943 0.219 0.034 8.49E−80 Cd5l 8.35E−84 0.460825248 0.199 0.026 2.07E−79 Cox6c 1.85E−83 −0.517417109 0.665 0.884 4.59E−79 Saa4 2.78E−83 0.635837715 0.804 0.749 6.90E−79 Ccnd1 2.52E−82 0.385849227 0.218 0.035 6.27E−78 Cyp2c54 9.56E−82 −0.542960224 0.426 0.759 2.37E−77 Serpina1a 1.36E−79 −0.35536875 0.932 0.991 3.38E−75 P4hb 6.98E−79 0.38506968 0.949 0.941 1.73E−74 Serpina1b 8.00E−79 −0.294480791 0.96 0.996 1.99E−74 Tmem176b 1.62E−78 0.612457008 0.744 0.632 4.03E−74 Gas6 2.14E−78 0.35878079 0.215 0.036 5.31E−74 Gm23935 8.90E−78 0.562414557 0.975 0.925 2.21E−73 Ahcy 3.00E−77 −0.455985571 0.701 0.916 7.46E−73 mt-Nd6 4.60E−77 −0.560268731 0.223 0.577 1.14E−72 Hmgcs1 1.63E−76 0.702526059 0.819 0.703 4.05E−72 Serpina1e 4.63E−76 −0.308360801 0.99 0.999 1.15E−71 Etnppl 1.08E−75 −0.549126978 0.257 0.606 2.68E−71 Aug 1.14E−75 0.644516227 0.773 0.687 2.84E−71 Marco 4.70E−75 0.30539135 0.106 0.002 1.17E−70 1500017E21Rik 7.78E−74 −0.517930222 0.164 0.476 1.93E−69 Ahsg 2.93E−73 0.281450293 0.998 1 7.29E−69 Atp5f1 4.47E−73 −0.460709866 0.681 0.869 1.11E−68 Ndufb6 1.65E−72 −0.479162745 0.49 0.759 4.11E−68 Ces1f 3.89E−71 −0.45903711 0.577 0.817 9.66E−67 Cebpa 1.18E−70 −0.481611184 0.37 0.672 2.92E−66 Cyp4a12a 4.03E−70 −0.4760363 0.275 0.597 1.00E−65 Baat 4.05E−70 −0.445833101 0.496 0.767 1.01E−65 Inmt 6.48E−70 −0.502414474 0.676 0.884 1.61E−65 Gm12744 6.80E−70 0.350643059 0.231 0.05 1.69E−65 Pon1 7.92E−69 −0.42825679 0.753 0.906 1.97E−64 Aldob 9.05E−69 −0.254127817 0.986 0.996 2.25E−64 Clu 1.45E−68 0.374886754 0.954 0.958 3.60E−64 Rbp1 2.09E−68 0.396801127 0.264 0.069 5.19E−64 Fabp2 2.20E−68 −0.488533591 0.305 0.622 5.45E−64 Serpina1c 4.97E−68 −0.279835146 0.948 0.998 1.24E−63 Sod1 6.75E−68 −0.277853669 0.952 0.983 1.68E−63 Cdo1 8.26E−68 −0.343333854 0.843 0.96 2.05E−63 Steap4 1.90E−67 0.631013696 0.455 0.222 4.71E−63 Cml1 2.23E−67 −0.47269345 0.507 0.757 5.55E−63 Ech1 1.04E−66 −0.414674796 0.617 0.856 2.57E−62 Insig2 1.92E−66 −0.447606183 0.554 0.81 4.77E−62 Cox6a1 6.74E−66 −0.390617907 0.665 0.887 1.67E−61 Azgp1 4.66E−65 −0.286918536 0.904 0.968 1.16E−60 Ces1c 2.36E−64 −0.274525359 0.96 0.985 5.85E−60 Pah 3.48E−64 −0.379853874 0.71 0.891 8.65E−60 C1qb 1.01E−63 0.361309767 0.163 0.024 2.50E−59 Lipc 1.28E−63 −0.423055461 0.294 0.59 3.19E−59 Dio1 3.68E−63 −0.469732353 0.255 0.542 9.15E−59 Aox3 4.95E−63 −0.429460462 0.705 0.894 1.23E−58 Gstm1 1.23E−62 −0.448355325 0.783 0.935 3.06E−58 Mgst1 1.50E−62 −0.286240934 0.997 0.997 3.71E−58 Rnf125 4.04E−62 −0.423361675 0.201 0.493 1.00E−57 Slc27a5 4.35E−62 −0.374625102 0.749 0.893 1.08E−57 Serpina3m 5.13E−62 0.519751144 0.76 0.722 1.28E−57 Amy1 5.64E−62 −0.441174 0.383 0.676 1.40E−57 Mki67 6.42E−62 0.39305852 0.086 0.001 1.59E−57 Tmem205 2.42E−61 −0.363762607 0.791 0.934 6.01E−57 Cyp2a12 2.80E−61 −0.396631721 0.664 0.884 6.96E−57 Acnat2 7.56E−61 0.33547101 0.252 0.069 1.88E−56 Angptl3 6.16E−60 −0.315601765 0.879 0.944 1.53E−55 Qsox1 9.01E−60 0.551776463 0.752 0.707 2.24E−55 Top2a 4.44E−59 0.33486876 0.09 0.003 1.10E−54 Cyp7b1 5.53E−59 −0.438158056 0.496 0.757 1.37E−54 Hpd 8.05E−59 −0.317943335 0.91 0.976 2.00E−54 Cyp3a25 9.34E−59 −0.34306526 0.745 0.919 2.32E−54 Ugp2 2.65E−58 −0.394209561 0.486 0.749 6.59E−54 Clpx 4.49E−58 −0.410840842 0.571 0.783 1.11E−53 Clec4f 4.74E−58 0.380337956 0.2 0.043 1.18E−53 Ndufa4 4.11E−57 −0.4035957 0.71 0.889 1.02E−52 Gm20594 4.89E−57 −0.573781187 0.048 0.294 1.21E−52 Cyp2c50 6.18E−57 −0.467298435 0.656 0.888 1.54E−52 Pzp 1.05E−56 0.382796555 0.975 0.986 2.61E−52 Nudt7 3.82E−56 −0.566043759 0.662 0.83 9.48E−52 Uqcrq 4.46E−56 −0.341869458 0.857 0.951 1.11E−51 Oaz1 5.13E−56 −0.426286153 0.499 0.75 1.27E−51 Rpl41 6.29E−56 0.444557582 0.528 0.278 1.56E−51 Cdca3 7.55E−56 0.286393603 0.1 0.007 1.87E−51 Slc10a1 3.28E−55 −0.395488081 0.688 0.843 8.15E−51 Ifitm2 4.32E−55 0.526891524 0.532 0.347 1.07E−50 Scp2 4.62E−55 −0.319519472 0.902 0.986 1.15E−50 Rps27l 3.21E−54 −0.377566144 0.632 0.849 7.98E−50 Sco2 4.20E−54 −0.395951512 0.24 0.508 1.04E−49 Esd 7.80E−54 −0.381539462 0.549 0.784 1.94E−49 Cyp2d10 1.51E−53 −0.325332653 0.742 0.921 3.76E−49 Ndufb11 2.89E−53 −0.398618793 0.471 0.735 7.18E−49 Chchd2 6.84E−53 −0.369755887 0.769 0.916 1.70E−48 Idh3b 1.69E−52 −0.360516268 0.387 0.655 4.19E−48 Dbi 3.82E−52 0.360631658 0.969 0.971 9.49E−48 Bckdha 9.15E−52 −0.404702898 0.365 0.63 2.27E−47 Glo1 1.41E−51 −0.379233492 0.498 0.749 3.51E−47 Glud1 1.89E−51 0.359099708 0.901 0.905 4.69E−47 M2 5.51E−51 −0.333366521 0.297 0.579 1.37E−46 Sdhb 1.01E−50 −0.357362255 0.577 0.797 2.51E−46 Cat 4.03E−50 −0.286016441 0.912 0.971 1.00E−45 Ces1e 8.30E−50 −0.356936678 0.304 0.576 2.06E−45 Tat 9.87E−50 0.369618242 0.91 0.903 2.45E−45 Cox5b 1.37E−49 −0.393691854 0.454 0.726 3.39E−45 Mup10 1.94E−49 0.281431551 0.781 0.692 4.82E−45 Aqp8 3.30E−49 −0.359788885 0.242 0.505 8.19E−45 Atp5g3 9.30E−49 −0.302277876 0.74 0.911 2.31E−44 Hint2 1.05E−48 −0.373773572 0.433 0.676 2.60E−44 Actb 1.06E−48 0.399035393 0.897 0.886 2.62E−44 Itm2b 1.69E−48 −0.261048932 0.869 0.951 4.20E−44 Cox7b 4.24E−48 −0.386524219 0.704 0.878 1.05E−43 Fmo5 7.05E−48 0.379271143 0.841 0.837 1.75E−43 Etfdh 7.29E−48 −0.33708519 0.436 0.7 1.81E−43 1100001G20Rik 1.66E−47 0.310291029 0.982 0.982 4.13E−43 Gsto1 2.07E−47 −0.368935961 0.269 0.52 5.15E−43 Sds 3.22E−47 −0.352238286 0.35 0.67 7.99E−43 Hsd3b3 1.54E−46 −0.347460551 0.359 0.605 3.82E−42 Slc27a2 8.99E−46 −0.305294922 0.812 0.949 2.23E−41 Hsd17b6 1.04E−45 −0.36218325 0.189 0.453 2.58E−41 Gm4076 1.16E−45 −0.345826319 0.001 0.184 2.87E−41 Mat1a 2.28E−45 0.378728792 0.938 0.966 5.65E−41 Abcd3 5.85E−45 −0.326838469 0.677 0.879 1.45E−40 Cyp2c37 6.44E−45 −0.412938667 0.326 0.608 1.60E−40 Mdh1 8.20E−45 −0.329025797 0.747 0.887 2.04E−40 Prdx4 1.37E−44 −0.378024564 0.368 0.607 3.39E−40 Hsd17b13 2.14E−44 −0.376251609 0.464 0.74 5.32E−40 Proc 6.67E−44 −0.319776879 0.696 0.874 1.66E−39 Agxt 7.21E−44 −0.303827932 0.555 0.789 1.79E−39 Gls2 8.71E−44 −0.353616749 0.395 0.657 2.16E−39 Cpb2 4.37E−43 0.395699062 0.838 0.813 1.09E−38 Ugt2b38 4.82E−43 −0.250921219 0.021 0.209 1.20E−38 Cyp2a5 5.97E−43 −0.525680085 0.295 0.555 1.48E−38 Ndufb9 8.65E−43 −0.291910914 0.729 0.888 2.15E−38 Cdc20 1.26E−42 0.272554242 0.062 0.001 3.12E−38 Rabac1 1.31E−42 −0.342063679 0.284 0.524 3.25E−38 Slc22a30 3.13E−42 −0.331870745 0.26 0.493 7.77E−38 Etfa 3.25E−42 −0.33793403 0.595 0.802 8.07E−38 Cd302 7.31E−42 0.384976006 0.864 0.86 1.82E−37 Csf1r 1.53E−41 0.284684372 0.106 0.015 3.79E−37 Cth 1.76E−41 −0.332234114 0.681 0.838 4.36E−37 Atp5j 2.00E−41 −0.302644835 0.512 0.757 4.96E−37 Uqcrfs1 2.26E−41 −0.335765197 0.583 0.787 5.60E−37 Cyp27a1 5.89E−41 −0.326228094 0.636 0.837 1.46E−36 Hal 1.22E−40 −0.304647432 0.47 0.749 3.02E−36 Ppp2r5a 1.36E−40 −0.315098874 0.366 0.594 3.37E−36 Sar1b 1.79E−40 −0.301891484 0.56 0.772 4.44E−36 Aldh6a1 1.87E−40 −0.30870904 0.471 0.704 4.64E−36 Il1rap 7.80E−40 −0.302807638 0.35 0.58 1.94E−35 S100a1 8.91E−40 −0.355544479 0.454 0.661 2.21E−35 Creg1 1.17E−39 −0.258963412 0.787 0.926 2.90E−35 Gstm2 1.61E−39 0.466218536 0.345 0.169 3.99E−35 Mbl2 2.21E−39 −0.254854549 0.625 0.829 5.49E−35 Apoc2 2.61E−39 0.517142972 0.803 0.802 6.48E−35 1300017J02Rik 4.81E−39 −0.308343818 0.59 0.803 1.20E−34 Acat1 7.30E−39 −0.290805818 0.628 0.838 1.81E−34 Pklr 2.19E−38 −0.283149611 0.157 0.368 5.43E−34 Krt18 2.37E−38 0.520354076 0.681 0.617 5.88E−34 Dpys 3.56E−38 −0.313405671 0.447 0.682 8.84E−34 Aadat 3.68E−38 −0.325731706 0.28 0.507 9.13E−34 Mup1 4.45E−38 −0.62326727 0.367 0.583 1.11E−33 Gm5096 5.11E−38 −0.336704156 0.249 0.468 1.27E−33 Cd81 6.03E−38 −0.30883572 0.435 0.675 1.50E−33 Ndufc2 6.26E−38 −0.370889898 0.371 0.579 1.56E−33 Bphl 6.83E−38 −0.299478155 0.355 0.579 1.70E−33 Qdpr 7.25E−38 −0.316595182 0.649 0.814 1.80E−33 Gsta2 1.84E−37 −0.284180552 0.129 0.333 4.56E−33 Acsm3 2.12E−37 −0.280708005 0.191 0.407 5.27E−33 Cyp2d26 8.21E−37 −0.270278674 0.755 0.903 2.04E−32 Cyp2c44 8.41E−37 −0.312764543 0.48 0.698 2.09E−32 Hagh 1.20E−36 −0.288430674 0.699 0.858 2.99E−32 Ndufa6 1.25E−36 −0.330965466 0.603 0.798 3.11E−32 Ces2a 1.73E−36 −0.288140076 0.628 0.846 4.30E−32 Fn1 2.06E−36 0.469732274 0.819 0.821 5.12E−32 Gm10250 2.24E−36 −0.304478582 0.068 0.251 5.57E−32 Gas5 2.54E−36 −0.298417518 0.294 0.527 6.31E−32 Alas1 3.08E−36 0.423999349 0.749 0.729 7.65E−32 Hebp1 3.34E−36 −0.297464234 0.539 0.75 8.29E−32 Uqcrb 5.39E−36 −0.339504918 0.425 0.641 1.34E−31 Gm4788 6.02E−36 −0.297042332 0.575 0.766 1.49E−31 Slc2a2 1.00E−35 −0.291267847 0.261 0.479 2.49E−31 Tmsb4x 3.03E−35 0.347657914 0.183 0.057 7.53E−31 Cela1 4.17E−35 −0.252611197 0.112 0.304 1.03E−30 Hgd 9.92E−35 −0.273998205 0.693 0.861 2.46E−30 Dnajc12 1.02E−34 0.312907586 0.256 0.108 2.54E−30 Gadd45g 1.32E−34 −0.336240737 0.402 0.639 3.29E−30 1110008F13Rik 1.52E−34 −0.284458511 0.424 0.648 3.77E−30 Csad 1.75E−34 −0.308703065 0.516 0.744 4.35E−30 Gabarapl1 8.13E−34 −0.297156374 0.563 0.779 2.02E−29 Eci1 1.80E−33 −0.292606814 0.482 0.709 4.47E−29 Sparcl1 2.40E−33 −0.253616986 0 0.136 5.97E−29 Atp5h 2.89E−33 −0.352362982 0.47 0.682 7.17E−29 Amdhd1 3.26E−33 −0.272469871 0.442 0.661 8.10E−29 Lyz2 4.87E−33 0.275390862 0.132 0.032 1.21E−28 Uqcrh 6.10E−33 −0.290259964 0.629 0.81 1.52E−28 0610011F06Rik 1.41E−32 −0.28593883 0.437 0.653 3.51E−28 Ftcd 2.20E−32 −0.299187456 0.473 0.691 5.47E−28 Cyp4f14 2.60E−32 −0.283565035 0.394 0.6 6.47E−28 BC048546 4.68E−32 0.287060939 0.265 0.119 1.16E−27 Ttc39c 9.43E−32 −0.289612311 0.454 0.642 2.34E−27 Mup14 9.56E−32 −0.497427273 0.421 0.616 2.38E−27 Ndufv1 9.79E−32 −0.256865664 0.462 0.683 2.43E−27 Pdhb 2.21E−31 −0.271619421 0.269 0.468 5.48E−27 Hsd17b11 3.37E−31 −0.272884574 0.379 0.592 8.36E−27 Gstm3 5.90E−31 0.793361403 0.543 0.414 1.46E−26 Fcgrt 7.31E−31 −0.270945405 0.382 0.599 1.81E−26 Arl4d 1.23E−30 −0.288941612 0.245 0.437 3.05E−26 Lyrm5 1.24E−30 −0.251171881 0.206 0.396 3.08E−26 Bnip3 1.25E−30 −0.275946132 0.335 0.55 3.10E−26 Pygl 5.20E−30 −0.25405228 0.572 0.776 1.29E−25 C8b 6.04E−30 −0.251084368 0.722 0.881 1.50E−25 Atp5j2 1.03E−29 −0.255051714 0.678 0.852 2.55E−25 Igfbp1 1.08E−29 0.466237818 0.716 0.717 2.67E−25 Fxyd1 1.19E−29 −0.273422293 0.499 0.721 2.95E−25 Slc41a2 2.25E−29 0.318516467 0.278 0.134 5.60E−25 Nit2 2.74E−29 −0.255321274 0.375 0.577 6.79E−25 Sdha 3.20E−29 −0.286156431 0.554 0.747 7.96E−25 Pccb 3.22E−29 −0.266663529 0.433 0.644 8.00E−25 Park7 3.63E−29 −0.270929309 0.572 0.784 9.02E−25 Cmbl 3.89E−29 −0.265365994 0.476 0.678 9.66E−25 Upp2 4.15E−29 −0.265836776 0.451 0.673 1.03E−24 Prg4 5.85E−29 0.355545985 0.344 0.188 1.45E−24 Itih2 9.24E−29 0.312933325 0.866 0.884 2.29E−24 Zfp683 2.98E−28 −0.421689112 0 0.116 7.40E−24 Ces2e 3.51E−28 −0.272708804 0.335 0.535 8.71E−24 Cebpb 6.97E−28 −0.306330499 0.272 0.45 1.73E−23 Pbld1 8.97E−28 −0.264627734 0.366 0.565 2.23E−23 Gm9843 3.14E−27 −0.298882573 0.135 0.299 7.79E−23 Adipor2 4.45E−27 −0.252551165 0.638 0.807 1.11E−22 Ephx1 5.06E−27 −0.261640077 0.589 0.8 1.26E−22 Pim3 1.08E−26 −0.255337561 0.345 0.537 2.68E−22 C6 8.21E−26 −0.255102014 0.434 0.642 2.04E−21 Hspa8 1.73E−25 0.302152434 0.744 0.756 4.31E−21 Rps2 8.86E−25 −0.269321392 0.544 0.757 2.20E−20 Ly6e 2.02E−24 0.525599776 0.49 0.386 5.02E−20 Txnip 5.00E−24 −0.310098222 0.142 0.297 1.24E−19 Dynll1 7.21E−24 0.289016997 0.283 0.154 1.79E−19 Cyp2e1 9.88E−24 −0.298608744 0.715 0.911 2.45E−19 Tspan4 1.37E−23 0.32084381 0.364 0.23 3.41E−19 Thrsp 6.26E−23 −0.374383397 0.497 0.627 1.55E−18 Il1r1 1.12E−22 0.299449962 0.301 0.167 2.79E−18 Kng2 1.19E−22 0.3169695 0.687 0.684 2.95E−18 2200002D01Rik 6.87E−22 0.257614019 0.261 0.136 1.71E−17 G6pc 1.49E−21 −0.259264856 0.597 0.752 3.71E−17 Cyp51 1.75E−21 0.40339747 0.67 0.649 4.34E−17 Cyp7a1 2.38E−21 0.598824806 0.372 0.259 5.91E−17 Tgm2 2.39E−20 0.37123494 0.374 0.258 5.94E−16 Mlec 5.88E−20 0.400321297 0.436 0.323 1.46E−15 Myh9 6.40E−20 0.438269269 0.426 0.318 1.59E−15 Smc4 1.53E−18 0.338338192 0.177 0.083 3.80E−14 Rn7sk 2.49E−18 −0.276399379 0.073 0.186 6.19E−14 Hrg 2.76E−18 0.270451116 0.807 0.831 6.86E−14 Snx10 5.15E−18 0.253822304 0.304 0.188 1.28E−13 Gm24245 1.34E−17 −0.264578368 0.097 0.214 3.33E−13 Eef1a1 5.03E−17 0.254969818 0.794 0.85 1.25E−12 Sdc1 5.77E−17 0.330139692 0.531 0.469 1.43E−12 Sult1a1 8.71E−17 0.344836675 0.69 0.707 2.16E−12 Ctsb 8.73E−17 0.310468937 0.777 0.781 2.17E−12 Hspa5 9.12E−17 0.270882455 0.929 0.944 2.27E−12 Gjb2 9.83E−17 0.328679811 0.61 0.572 2.44E−12 Dap 1.60E−16 0.290008119 0.667 0.654 3.97E−12 Slc3a1 7.18E−16 0.321802388 0.29 0.189 1.78E−11 Hsph1 4.12E−15 0.345997935 0.353 0.255 1.02E−10 Mrap 4.18E−15 0.280974611 0.376 0.272 1.04E−10 Grn 1.80E−14 0.293077345 0.48 0.396 4.47E−10 Lpgat1 4.23E−14 0.347767347 0.545 0.502 1.05E−09 Creld2 4.49E−13 0.362477611 0.385 0.296 1.11E−08 Cpox 1.20E−12 0.294319953 0.513 0.45 2.98E−08 Ftl1 6.02E−12 −0.259151442 0.298 0.409 1.49E−07 Ebp 1.48E−11 0.252819864 0.634 0.666 3.69E−07 Fdps 1.57E−10 0.303232732 0.492 0.445 3.91E−06 Btg2 9.56E−10 0.280923811 0.321 0.241 2.37E−05 Gm26917 1.01E−09 0.475554164 0.255 0.181 2.52E−05 Lrp1 1.11E−09 0.314138344 0.597 0.591 2.75E−05 Stat3 1.14E−09 0.308012615 0.386 0.318 2.82E−05 Ugdh 1.89E−09 0.260443532 0.602 0.604 4.68E−05 Tmpo 2.13E−09 0.2573532 0.236 0.162 5.30E−05 Cxcl1 2.93E−09 0.353012683 0.374 0.314 7.28E−05 Lss 5.24E−09 0.294433908 0.282 0.211       0.000130068 Hyou1 6.67E−09 0.315760783 0.44 0.385       0.000165574 Akr1d1 1.25E−08 0.258293189 0.537 0.515      0.00030931 Snord13 1.32E−08 0.408788625 0.247 0.175       0.000327047 Acsl4 1.24E−07 0.273275871 0.376 0.323       0.003086449 Lsr 2.32E−07 0.262580416 0.512 0.517       0.005770468 Tuba1c 2.44E−07 0.302939755 0.415 0.37       0.006056912 Caprin1 6.74E−07 0.303020851 0.497 0.481       0.016747307 Atl3 8.51E−07 0.255322039 0.334 0.27       0.021123411 Manf 9.37E−07 0.282950631 0.466 0.44       0.023268676 Txnrd1 1.31E−06 0.252234489 0.468 0.441       0.032529357 Avpi1 4.09E−06 0.30186919 0.409 0.377       0.101466193 Krt8 7.36E−06 0.252276759 0.552 0.578       0.182829207 Sqle 5.87E−05 0.27714068 0.379 0.349 1 Nucks1 9.19E−05 0.271055696 0.445 0.43 1 Lect2       0.000105656 0.288512824 0.427 0.414 1 Oat       0.000221224 0.741679089 0.542 0.611 1 Tubb5      0.00072943 0.313824522 0.304 0.271 1 Tubb4b       0.032455023 0.28149027 0.347 0.343 1 Glul       0.033844352 0.611936929 0.203 0.18 1

TABLE 7 Differentially Expressed genes between timepoint PH120 and Untreated (UT) p_val avg_logFC pct. 1 pct. 2 p_val_adj Saa2 0 3.598008691 0.948 0.222 0 Saa1 0 2.959370227 0.996 0.662 0 Lcn2 0 2.127649068 0.925 0.07 0 Mt1 0 1.65972779 0.975 0.556 0 Orm2 0 1.536747401 0.813 0.09 0 Gm15564 0 1.485885928 1 0.956 0 Mt2 0 1.471840722 0.93 0.365 0 Lars2 0 1.419129056 1 0.994 0 Fgl1 0 1.379926505 0.993 0.784 0 Gm26924 0 1.379756734 1 1 0 Lrg1 0 1.260509735 0.982 0.736 0 Serpina3n 0 1.205364333 0.948 0.574 0 Itih4 0 1.18011817 0.998 0.948 0 Itih3 0 1.177912468 0.991 0.89 0 Saa4 0 1.158596154 0.982 0.749 0 Hp 0 1.107075607 0.999 0.999 0 Ly6e 0 1.093957206 0.821 0.386 0 C3 0 1.071950932 0.999 0.99 0 n-R5-8s1 0 1.066654791 0.578 0.031 0 Orm1 0 1.05827481 1 0.952 0 Fga 0 1.039432587 0.999 0.997 0 Rnase4 0 1.031156304 0.993 0.921 0 Fn1 0 1.018772906 0.968 0.821 0 Hpx 0 0.994363825 1 0.997 0 Cfh 0 0.83288399 0.991 0.897 0 C4b 0 0.820022988 0.98 0.883 0 Clu 0 0.745288027 0.997 0.958 0 Fgg 0 0.686743278 1 0.991 0 Gm24601 0 0.675086715 0.422 0.015 0 Pzp 0 0.636851805 0.999 0.986 0 Fgb 0 0.605783409 0.999 1 0 Plg 0 0.596524395 0.997 0.961 0 Kng1 0 0.546835494 0.999 0.991 0 Serpina1e 0 −0.72519719 0.993 0.999 0 Cyp3a11 0 −0.803553063 0.997 1 0 Fabp1 0 −0.826491833 0.995 1 0 mt-Rnr1 0 −0.844781496 1 1 0 Acaa1b 0 −0.855527427 0.792 0.969 0 mt-Rnr2 0 −0.967453486 1 1 0 Mup20 0 −1.081531043 0.99 1 0 Car3 0 −1.168630683 0.905 0.974 0 Ces1d 0 −1.201503329 0.586 0.923 0 Mup12 0 −1.228078411 0.39 0.86 0 Mup16 0 −1.245137265 0.578 0.934 0 Mup3 0 −1.310718039 1 1 0 mt-Nd2 0 −1.350784061 0.975 0.999 0 mt-Nd5 0 −1.49645814 0.9 0.995 0 mt-Nd1 0 −1.543996447 0.98 1 0 mt-Cytb 0 −1.554026854 0.965 0.999 0 mt-Co1 0 −1.569950123 0.956 0.999 0 Mup21 0 −1.637812283 0.302 0.929 0 Mup11 0 −1.769206667 0.949 1 0 Mup5 0 −1.774609558 0.261 0.839 0 Mup4 0 −1.909428244 0.231 0.898 0 mt-Nd4 0 −1.953205815 0.909 0.998 0 Mup17 0 −2.382123881 0.798 1 0 Mup9 0 −2.520658851 0.309 0.976 0 Mup18 0 −2.585635085 0.505 0.997 0 Mup6 0 −2.588052175 0.543 0.992 0 Mup19 0 −3.348975652 0.594 1 0 Gm23935  5.57E−302 1.207244314 0.997 0.925  1.38E−297 Vtn  3.61E−298 0.516935534 0.998 0.983  8.96E−294 Cp  2.34E−294 0.655511152 0.995 0.943  5.81E−290 Ugt2b5  2.32E−293 −0.716336886 0.923 0.959  5.77E−289 Cyb5  8.57E−293 −0.751689441 0.984 0.983  2.13E−288 Gm13775  2.16E−292 −1.171528238 0.197 0.761  5.37E−288 Ambp  2.76E−292 0.496213815 0.999 0.993  6.84E−288 Steap4  5.28E−289 0.931387724 0.71 0.222  1.31E−284 mmu-mir-6236  2.07E−288 1.257248389 0.989 0.837  5.14E−284 Apoa2  4.19E−281 −0.42773886 0.999 1  1.04E−276 Apcs  2.39E−279 0.965147497 0.879 0.525  5.94E−275 mt-Co2  4.87E−279 −1.39473643 0.04 0.629  1.21E−274 Rbp4  1.82E−274 −0.451760058 0.998 0.999  4.52E−270 Mup15  2.40E−272 −1.359329494 0.038 0.617  5.96E−268 Csad  2.12E−271 −1.214863323 0.237 0.744  5.27E−267 Apoa1  2.66E−257 −0.411233725 1 1  6.60E−253 Gsta3  1.24E−254 −0.796926805 0.94 0.956  3.08E−250 Mat1a  1.17E−250 0.519634823 0.998 0.966  2.90E−246 Prg4  3.37E−248 0.810835665 0.643 0.188  8.36E−244 Serpina3k  1.13E−246 −0.298266533 1 1  2.79E−242 Qsox1  9.01E−246 0.725062115 0.93 0.707  2.24E−241 Lrp1  8.74E−236 0.914046975 0.874 0.591  2.17E−231 Serpina10  5.42E−235 0.740578005 0.896 0.641  1.35E−230 Elovl3  6.32E−234 −0.924845607 0.48 0.827  1.57E−229 mt-Co3  1.22E−233 −1.229639242 0.097 0.603  3.03E−229 Tmem176b  1.30E−230 0.713749974 0.901 0.632  3.22E−226 Ahsg  1.31E−226 0.32482682 1 1  3.27E−222 Aldh1l1  2.28E−225 0.564932962 0.989 0.904  5.65E−221 Sod1  1.28E−220 −0.483374172 0.983 0.983  3.17E−216 Retsat  1.74E−220 −0.847260321 0.524 0.83  4.31E−216 Pck1  3.48E−214 0.495042924 0.999 0.987  8.65E−210 Hrg  1.60E−213 0.58732025 0.966 0.831  3.97E−209 Hc  9.30E−212 0.611232959 0.974 0.903  2.31E−207 Prtn3  1.80E−209 0.350182853 0.271 0.003  4.48E−205 Scd1  1.49E−208 0.787835318 0.996 0.901  3.71E−204 Egfr  1.72E−203 0.65440823 0.964 0.809  4.26E−199 Tat  1.58E−198 0.614979826 0.988 0.903  3.93E−194 Orm3  4.42E−196 0.517250103 0.47 0.093  1.10E−191 Tmem176a  5.12E−195 0.67082422 0.773 0.429  1.27E−190 Igfbp2  1.45E−194 −0.717832911 0.644 0.885  3.60E−190 Ankrd55  1.65E−189 −1.470505577 0.312 0.696  4.09E−185 Cyp2c29  1.46E−188 −0.997502622 0.799 0.93  3.62E−184 Apoc4  4.78E−187 −0.501759591 0.98 0.98  1.19E−182 Sephs2  7.48E−187 0.604852301 0.928 0.761  1.86E−182 Serping1  1.42E−183 0.535830748 0.964 0.87  3.54E−179 Il1r1  1.89E−181 0.63980318 0.558 0.167  4.69E−177 Mpeg1  1.71E−178 0.541170007 0.435 0.089  4.24E−174 Lbp  5.79E−176 0.656662588 0.702 0.333  1.44E−171 Angptl3  1.07E−173 −0.529458826 0.922 0.944  2.66E−169 Cyp2b10  4.98E−173 −1.247317124 0.138 0.542  1.24E−168 Cox4i1  8.99E−173 −0.518813262 0.938 0.958  2.23E−168 Mup13  2.53E−169 −0.875079323 0.129 0.546  6.29E−165 Rps14  1.51E−156 −0.607507888 0.793 0.917  3.76E−152 Apob  1.86E−155 0.505397578 0.997 0.989  4.63E−151 Cyp2c70  2.58E−154 0.511802822 0.967 0.834  6.40E−150 Ctsb  1.82E−153 0.553974491 0.927 0.781  4.51E−149 C4bp  4.59E−153 0.505363658 0.934 0.788  1.14E−148 Ifitm3  1.15E−152 0.506857449 0.944 0.812  2.86E−148 Cox7b  1.35E−148 −0.650085753 0.747 0.878  3.36E−144 Tifa  1.62E−148 0.321485305 0.297 0.036  4.02E−144 Cml2  2.92E−147 0.486040271 0.953 0.857  7.24E−143 Mup7  3.24E−146 −0.844127621 0.967 0.998  8.04E−142 Itih1  5.47E−146 0.496617676 0.936 0.816  1.36E−141 Myh9  1.14E−145 0.631035657 0.652 0.318  2.83E−141 Ces2a  3.16E−145 −0.619093582 0.652 0.846  7.84E−141 Rps27l  5.72E−144 −0.64582348 0.684 0.849  1.42E−139 Inmt  6.28E−144 −0.679790467 0.791 0.884  1.56E−139 Cd5l  1.89E−142 0.49371428 0.263 0.026  4.68E−138 mt-Atp6  1.26E−138 −0.875890108 0.083 0.452  3.13E−134 Hspb8  1.70E−137 0.52383406 0.837 0.597  4.23E−133 P4hb  5.28E−137 0.369961971 0.99 0.941  1.31E−132 Cox6c  9.25E−137 −0.610222852 0.753 0.884  2.30E−132 Dhcr24  5.84E−135 0.551421264 0.92 0.783  1.45E−130 Cyp2c37  8.45E−135 −0.820386118 0.239 0.608  2.10E−130 Mgst1  8.85E−134 −0.36875402 0.998 0.997  2.20E−129 Igfbp4  5.12E−133 0.411174683 0.952 0.866  1.27E−128 Ang  1.34E−132 0.599634512 0.874 0.687  3.32E−128 Slc41a2  1.76E−131 0.441321771 0.446 0.134  4.36E−127 Creg1  6.09E−130 −0.480113825 0.87 0.926  1.51E−125 Uqcrq  9.76E−129 −0.485354968 0.922 0.951  2.42E−124 Serpina3c  1.89E−128 −0.595568461 0.042 0.385  4.68E−124 Comt  8.75E−128 0.384473508 0.987 0.931  2.17E−123 Akr1c6  1.28E−127 −0.457641734 0.974 0.971  3.18E−123 Mup8  1.53E−127 −0.82718199 0.033 0.373  3.80E−123 Cyp8b1  6.21E−125 −0.599290325 0.449 0.745  1.54E−120 Chchd2  4.44E−124 −0.518624159 0.844 0.916  1.10E−119 Clec4f  6.98E−124 0.487336922 0.282 0.043  1.73E−119 Calr  6.49E−121 0.391955529 0.961 0.885  1.61E−116 Ahcy  6.32E−120 −0.49011253 0.819 0.916  1.57E−115 Mup2  2.15E−119 −0.72405868 0.064 0.392  5.33E−115 Cyp2c54  5.72E−119 −0.632023168 0.475 0.759  1.42E−114 Ech1  9.40E−119 −0.504022226 0.722 0.856  2.34E−114 Scara5  1.06E−118 0.285535495 0.301 0.054  2.62E−114 Cfi  8.71E−118 0.390834066 0.97 0.905  2.16E−113 Mug2  1.37E−117 0.536577024 0.881 0.738  3.40E−113 Ces1f  3.73E−116 −0.533638921 0.676 0.817  9.25E−112 H6pd  4.05E−116 0.491965789 0.8 0.595  1.01E−111 Gas6  7.61E−115 0.269480866 0.253 0.036  1.89E−110 mt-Nd6  1.11E−114 −0.685505467 0.245 0.577  2.74E−110 Hnf4a  1.24E−114 0.470873585 0.887 0.743  3.08E−110 Slc39a14  4.67E−113 0.506662289 0.638 0.343  1.16E−108 Ndufa4  1.67E−111 −0.512722876 0.803 0.889  4.13E−107 Ugt2b34  4.49E−111 −0.500802828 0.776 0.874  1.12E−106 H2-D1  4.57E−110 0.433183706 0.911 0.774  1.14E−105 Lpl  7.13E−110 0.355011922 0.194 0.016  1.77E−105 Mup10  1.62E−109 0.254194035 0.893 0.692  4.03E−105 Ndufb9  4.31E−109 −0.483703094 0.78 0.888  1.07E−104 Rbp1  6.28E−109 0.32795786 0.308 0.069  1.56E−104 Dap  2.21E−107 0.465257779 0.842 0.654  5.49E−103 Col18a1  2.40E−107 0.459095159 0.903 0.79  5.95E−103 Tdo2  1.13E−106 −0.283022598 0.991 0.991  2.80E−102 Wfdc17  5.33E−106 0.317329894 0.195 0.018  1.32E−101 Hint1  3.71E−105 −0.487016283 0.737 0.858  9.22E−101 Cpb2  1.34E−104 0.403790403 0.946 0.813  3.34E−100 C1qb  2.56E−104 0.337494489 0.208 0.024  6.35E−100 Rpl13a  9.02E−104 −0.480174283 0.747 0.868 2.24E−99 Cyp3a25  1.85E−103 −0.416456818 0.851 0.919 4.60E−99 Hspa5  4.12E−103 0.339769129 0.991 0.944 1.02E−98 Stat3  7.07E−103 0.483904634 0.602 0.318 1.75E−98 Fetub  7.47E−103 0.425407474 0.866 0.703 1.86E−98 Nnmt  2.70E−102 0.508818069 0.877 0.716 6.69E−98 C8a  1.21E−100 0.404198047 0.964 0.887 3.00E−96 Hsp90ab1 4.69E−99 0.323037124 0.977 0.922 1.17E−94 Lyz2 1.34E−97 0.402735723 0.222 0.032 3.33E−93 Slco1a1 2.66E−96 −0.542407867 0.584 0.777 6.62E−92 Ephx2 4.78E−96 −0.398908219 0.874 0.937 1.19E−91 Mup1 7.17E−96 −0.882906956 0.306 0.583 1.78E−91 Hyou1 1.36E−95 0.496156079 0.65 0.385 3.39E−91 Gstp1 1.73E−94 −0.671664785 0.644 0.822 4.28E−90 Isyna1 1.08E−93 0.270110032 0.218 0.034 2.67E−89 Slc25a15 1.65E−93 0.393990477 0.896 0.738 4.09E−89 Scrpinf2 3.06E−92 0.361403772 0.944 0.843 7.60E−88 Etnppl 6.39E−92 −0.566620392 0.312 0.606 1.59E−87 H2-Q10 1.82E−91 0.250632773 0.999 0.982 4.52E−87 Ugt2b36 1.93E−91 −0.355795521 0.924 0.93 4.78E−87 Hrsp12 2.78E−91 −0.395396316 0.898 0.939 6.91E−87 Acsl1 5.10E−90 −0.417030322 0.855 0.924 1.27E−85 Ndufb6 1.60E−89 −0.518384931 0.603 0.759 3.96E−85 Slc25a25 8.79E−89 0.442662636 0.866 0.704 2.18E−84 Gnmt 3.48E−88 −0.288175489 0.996 0.988 8.65E−84 Uqcrh 2.37E−87 −0.483113531 0.66 0.81 5.89E−83 Aldh2 2.96E−86 0.296492218 0.992 0.973 7.35E−82 Kng2 7.60E−86 0.368809413 0.833 0.684 1.89E−81 Serpina1a 2.51E−85 −0.295262554 0.986 0.991 6.23E−81 Cyp3a13 2.58E−85 0.420680082 0.774 0.569 6.41E−81 Sc4mol 4.25E−85 −0.519568919 0.409 0.642 1.06E−80 Slc38a3 1.97E−84 0.353500212 0.936 0.858 4.90E−80 Igfbp1 4.63E−83 0.488899754 0.849 0.717 1.15E−78 Atp5g3 7.53E−83 −0.357248453 0.841 0.911 1.87E−78 Cyp2c50 9.57E−83 −0.516529985 0.762 0.888 2.38E−78 Atp5f1 4.44E−82 −0.428496879 0.827 0.869 1.10E−77 Cps1 3.38E−81 0.312297912 0.991 0.971 8.39E−77 Cyp2d9 6.27E−81 −0.3250388 0.959 0.959 1.56E−76 Fabp2 1.06E−80 −0.527186942 0.377 0.622 2.63E−76 Uroc1 1.61E−80 0.459322934 0.782 0.615 3.99E−76 F5 4.28E−80 0.436709177 0.84 0.728 1.06E−75 Ldhd 4.17E−79 0.387086477 0.766 0.575 1.04E−74 Sdc4 8.45E−79 0.315436107 0.956 0.867 2.10E−74 2810007J24Rik 3.11E−78 −0.337772907 0.919 0.943 7.72E−74 Hsph1 7.72E−78 0.425977247 0.512 0.255 1.92E−73 Prdx1 9.13E−78 −0.353764247 0.914 0.927 2.27E−73 Rpl32 1.78E−77 −0.498592915 0.574 0.757 4.42E−73 Hagh 1.79E−77 −0.398106396 0.799 0.858 4.45E−73 Selenbp2 2.34E−77 −0.354512086 0.905 0.937 5.81E−73 Fmo5 2.40E−77 0.337493236 0.927 0.837 5.95E−73 Eef2 4.10E−77 0.321705764 0.937 0.873 1.02E−72 Ugt2a3 1.19E−76 −0.457903234 0.637 0.773 2.95E−72 Pcx 1.34E−76 0.367136085 0.832 0.661 3.33E−72 Fah 6.06E−76 0.325518495 0.926 0.834 1.51E−71 Hdlbp 1.02E−75 0.394030651 0.856 0.713 2.52E−71 Tmsb4x 5.25E−75 0.341035762 0.24 0.057 1.30E−70 Gjb2 7.57E−75 0.402811227 0.763 0.572 1.88E−70 Ndufb11 8.48E−75 −0.479044618 0.56 0.735 2.10E−70 Bhlhe40 4.96E−74 0.370112004 0.5 0.251 1.23E−69 Glud1 5.22E−74 0.307823999 0.972 0.905 1.30E−69 Cyp2a5 7.78E−74 −0.869524548 0.311 0.555 1.93E−69 Aadac 2.54E−73 −0.466442698 0.84 0.86 6.31E−69 Xdh 5.78E−73 0.373181784 0.507 0.258 1.44E−68 Acox1 7.26E−73 0.292890336 0.986 0.966 1.80E−68 Btg2 1.08E−72 0.386164963 0.484 0.241 2.69E−68 Mpc2 1.09E−72 −0.39520967 0.763 0.857 2.71E−68 Sar1b 2.65E−72 −0.422088437 0.655 0.772 6.58E−68 Atp5h 3.22E−72 −0.555498653 0.496 0.682 7.99E−68 Mup14 3.43E−72 −0.741008747 0.407 0.616 8.52E−68 Rps2 1.31E−71 −0.474519664 0.579 0.757 3.26E−67 Abhd2 5.22E−71 0.267241512 0.313 0.105 1.30E−66 Atp5j2 1.30E−70 −0.409576712 0.755 0.852 3.23E−66 Ugt1a1 2.13E−70 0.370092558 0.526 0.283 5.30E−66 Atp5j 2.88E−70 −0.415380683 0.594 0.757 7.16E−66 Lpgat1 4.21E−69 0.400787984 0.705 0.502 1.05E−64 Lpin1 1.83E−68 0.382955017 0.552 0.31 4.53E−64 Cyr61 3.89E−68 0.302881921 0.3 0.102 9.66E−64 Cfhr2 4.10E−68 −0.428849834 0.845 0.868 1.02E−63 Slc7a2 1.08E−66 0.374380964 0.846 0.735 2.68E−62 Uqcr11 3.45E−65 −0.368070557 0.805 0.879 8.58E−61 Gstm1 6.97E−65 −0.35224443 0.898 0.935 1.73E−60 Pros1 1.21E−64 0.26812884 0.38 0.158 3.01E−60 Slc22a7 5.79E−64 0.307857498 0.405 0.186 1.44E−59 Tgm2 1.02E−63 0.342526865 0.487 0.258 2.52E−59 Cox7a2 1.32E−63 −0.441101884 0.686 0.784 3.27E−59 Ndufa6 1.53E−63 −0.418444742 0.71 0.798 3.80E−59 Il6st 1.35E−62 0.382881893 0.503 0.273 3.35E−58 Hsd3b5 1.66E−62 −0.506259792 0.377 0.587 4.13E−58 Pon1 9.77E−62 −0.32604762 0.857 0.906 2.43E−57 Ctss 1.08E−61 0.270183132 0.137 0.019 2.68E−57 Plxnb2 1.84E−61 0.381208682 0.54 0.315 4.58E−57 Gne 1.85E−61 0.355262513 0.673 0.469 4.60E−57 Abcb11 2.10E−61 0.351857633 0.877 0.791 5.21E−57 Cpn2 2.42E−61 0.349996687 0.795 0.667 6.01E−57 Rps3 2.86E−61 −0.339903958 0.811 0.874 7.09E−57 Gm4076 3.05E−60 −0.342316728 0.007 0.184 7.57E−56 Ndufb8 5.90E−60 −0.389897205 0.594 0.746 1.46E−55 Slc3a1 1.04E−59 0.381791335 0.393 0.189 2.59E−55 Lgals9 1.46E−59 0.327550674 0.912 0.793 3.63E−55 Mtss1 4.52E−59 0.339863924 0.649 0.454 1.12E−54 Hamp2 7.68E−59 0.337201585 0.231 0.07 1.91E−54 Thrsp 1.73E−58 −0.629247506 0.503 0.627 4.31E−54 Etfb 1.94E−58 −0.270014172 0.925 0.94 4.81E−54 Psap 2.13E−58 0.318472244 0.709 0.513 5.30E−54 Mafb 4.64E−58 0.356246663 0.553 0.33 1.15E−53 Cd36 9.49E−58 0.291074527 0.318 0.123 2.36E−53 Pdia3 1.35E−57 0.276156858 0.879 0.797 3.36E−53 Habp2 1.41E−57 0.313462443 0.61 0.413 3.50E−53 Hmgcs1 2.77E−57 −0.387891871 0.552 0.703 6.89E−53 Hsd11b1 2.80E−57 −0.332361427 0.85 0.875 6.95E−53 Abca1 8.71E−57 0.370856836 0.594 0.377 2.16E−52 Cyp2c55 8.91E−57 −0.347841415 0.05 0.243 2.21E−52 Apon 1.18E−56 0.318989204 0.811 0.666 2.92E−52 Nbr1 1.91E−56 0.337157409 0.613 0.413 4.73E−52 Slc25a23 1.74E−55 0.332651576 0.603 0.399 4.31E−51 Malat1 1.79E−55 −0.41172143 0.568 0.78 4.45E−51 Gm26917 2.88E−55 0.443747552 0.374 0.181 7.15E−51 Leap2 5.13E−55 −0.404792721 0.438 0.632 1.27E−50 Cyp4a10 3.93E−54 −0.453214203 0.455 0.657 9.75E−50 F9 7.01E−54 0.303980935 0.784 0.632 1.74E−49 Mtus1 1.70E−53 0.385483144 0.615 0.42 4.23E−49 Kmo 1.83E−53 0.305370487 0.836 0.732 4.54E−49 Iigp1 1.99E−53 0.305889089 0.861 0.759 4.95E−49 Agt 2.00E−53 0.258205872 0.891 0.817 4.95E−49 Gns 3.76E−53 0.323226146 0.497 0.288 9.33E−49 Serpina3m 1.13E−52 0.305171041 0.835 0.722 2.80E−48 Cth 1.59E−52 −0.339209942 0.806 0.838 3.95E−48 Bsg 2.32E−52 0.273171859 0.892 0.797 5.75E−48 Scarb1 2.46E−52 0.32724782 0.552 0.358 6.10E−48 Got1 2.96E−52 0.331700716 0.753 0.587 7.35E−48 Grn 4.53E−52 0.316049742 0.597 0.396 1.12E−47 Uqcr10 7.78E−52 −0.382321788 0.679 0.8 1.93E−47 Aass 1.49E−51 0.312355615 0.836 0.716 3.70E−47 Arhgef26 1.82E−51 0.276634335 0.406 0.203 4.52E−47 Man2a1 4.79E−51 0.323273082 0.741 0.583 1.19E−46 Akr1c19 5.32E−51 −0.38253326 0.342 0.527 1.32E−46 Ddt 5.65E−51 −0.345838673 0.703 0.829 1.40E−46 Hsd17b6 3.80E−50 −0.364685233 0.224 0.453 9.45E−46 Gm9843 3.82E−50 −0.396322103 0.112 0.299 9.49E−46 Eef1b2 7.65E−50 −0.367328377 0.693 0.78 1.90E−45 Serpina12 7.73E−50 −0.404557025 0.273 0.492 1.92E−45 Sardh 1.19E−49 0.28626336 0.911 0.838 2.96E−45 Esd 2.03E−49 −0.338909518 0.682 0.784 5.03E−45 Gm10250 4.47E−49 −0.336847064 0.074 0.251 1.11E−44 Slc38a2 5.38E−49 0.333158401 0.609 0.413 1.34E−44 Edem1 7.34E−49 0.301212478 0.614 0.429 1.82E−44 Abat 9.75E−49 0.305043176 0.808 0.677 2.42E−44 Creld2 2.38E−48 0.307177214 0.499 0.296 5.90E−44 Ifitm2 3.24E−48 0.281474354 0.538 0.347 8.05E−44 Cyp2d10 3.72E−48 −0.26237727 0.857 0.921 9.23E−44 Dpyd 3.81E−48 0.315635393 0.792 0.659 9.45E−44 Ces1e 3.91E−48 −0.375733204 0.391 0.576 9.70E−44 Tnfrsf1a 7.65E−48 0.267537895 0.447 0.244 1.90E−43 Alas1 8.49E−48 0.300367757 0.867 0.729 2.11E−43 Chchd10 2.10E−47 −0.28090926 0.935 0.944 5.22E−43 Cox5b 2.10E−47 −0.373464063 0.569 0.726 5.23E−43 Myo18a 5.21E−47 0.253700048 0.409 0.211 1.29E−42 Sparcl1 8.10E−47 −0.253616986 0 0.136 2.01E−42 St6gal1 1.18E−46 0.295334926 0.417 0.226 2.92E−42 Tapbp 1.11E−45 0.265071778 0.464 0.263 2.77E−41 Cox6a1 1.73E−45 −0.275276508 0.833 0.887 4.29E−41 Rps24 2.78E−45 −0.386464837 0.472 0.637 6.91E−41 Ifih1 4.04E−45 0.264296168 0.383 0.195 1.00E−40 Copa 1.91E−44 0.294256247 0.559 0.363 4.75E−40 B3galt1 3.47E−44 0.251993915 0.343 0.163 8.61E−40 BC025446 1.79E−43 0.266911384 0.497 0.306 4.46E−39 Pcdh1 3.18E−43 0.265458741 0.411 0.222 7.89E−39 Eif4g2 3.25E−43 0.287105046 0.807 0.678 8.07E−39 Ephx1 1.05E−42 −0.332038055 0.694 0.8 2.60E−38 Acot1 1.07E−42 −0.299327096 0.07 0.237 2.65E−38 1300002K09Rik 7.15E−42 0.30148927 0.673 0.514 1.78E−37 Plec 8.20E−42 0.267122123 0.364 0.186 2.04E−37 Rpl14 8.70E−42 −0.357060958 0.403 0.574 2.16E−37 Caprin1 1.14E−41 0.295892842 0.644 0.481 2.84E−37 Gm5096 3.78E−41 −0.350534749 0.291 0.468 9.38E−37 Uba1 7.69E−41 0.281371963 0.579 0.416 1.91E−36 Hacl1 1.10E−40 −0.294916761 0.749 0.797 2.73E−36 Kynu 1.18E−40 0.28095477 0.728 0.588 2.94E−36 Rxra 2.31E−40 0.264560061 0.713 0.574 5.74E−36 Tfr2 3.41E−40 0.268628506 0.761 0.633 8.48E−36 Ctnnd1 5.70E−40 0.252846161 0.398 0.217 1.41E−35 Zfp683 1.26E−39 −0.421689112 0 0.116 3.13E−35 Fndc3a 2.93E−39 0.273177056 0.458 0.277 7.28E−35 Cpt1a 4.79E−39 0.276570679 0.763 0.651 1.19E−34 Rps18 4.80E−39 −0.415076007 0.422 0.578 1.19E−34 Gm20594 5.36E−39 −0.496964367 0.131 0.294 1.33E−34 1110008F13Rik 5.70E−39 −0.327482854 0.51 0.648 1.42E−34 Glo1 6.38E−39 −0.317338548 0.644 0.749 1.59E−34 Adh4 7.50E−39 0.282357284 0.676 0.521 1.86E−34 Cyp3a44 9.72E−39 −0.297417766 0.043 0.183 2.41E−34 Ugt2b1 6.39E−38 −0.261758027 0.835 0.871 1.59E−33 Ndufb4 8.62E−38 −0.331687642 0.322 0.49 2.14E−33 C130074G19Rik 1.30E−37 0.255729195 0.603 0.439 3.22E−33 Ptprf 1.81E−37 0.27768605 0.628 0.464 4.49E−33 Uqcrb 2.44E−37 −0.359656695 0.508 0.641 6.07E−33 Arhgef12 5.06E−37 0.304865834 0.573 0.408 1.26E−32 Sdhd 9.94E−37 −0.302302961 0.565 0.677 2.47E−32 Hint2 1.37E−36 −0.33360366 0.569 0.676 3.41E−32 Osbpl9 4.27E−36 0.270713808 0.598 0.448 1.06E−31 Vwa8 6.13E−36 0.262040545 0.489 0.311 1.52E−31 Oaz1 6.73E−36 −0.327014451 0.679 0.75 1.67E−31 Cyp51 2.31E−35 −0.324000937 0.523 0.649 5.74E−31 Plcxd2 2.57E−35 0.266285463 0.509 0.332 6.38E−31 Ndufc2 3.99E−35 −0.371342649 0.458 0.579 9.91E−31 Rps5 4.72E−35 −0.25674004 0.84 0.873 1.17E−30 Ndufb2 4.85E−35 −0.336855533 0.491 0.629 1.21E−30 Serpina6 4.89E−35 0.269623074 0.463 0.296 1.21E−30 Blvrb 8.86E−35 −0.351075319 0.409 0.564 2.20E−30 Eci1 1.50E−34 −0.31335345 0.592 0.709 3.71E−30 Slc10a1 1.69E−34 −0.273026083 0.836 0.843 4.19E−30 Mbl2 2.61E−34 0.268002193 0.924 0.829 6.49E−30 Rnf125 3.23E−34 −0.310633092 0.337 0.493 8.03E−30 Ndufs6 8.29E−34 −0.341035035 0.627 0.724 2.06E−29 Cnbp 9.89E−34 −0.286746587 0.71 0.778 2.46E−29 Atp2a2 1.78E−33 0.263222967 0.645 0.495 4.42E−29 Cyp4a14 4.43E−33 −0.31778609 0.253 0.431 1.10E−28 Prdx4 6.99E−33 −0.339424675 0.491 0.607 1.74E−28 Pid1 9.26E−33 0.263310286 0.549 0.381 2.30E−28 Txn1 2.60E−32 −0.277353299 0.75 0.809 6.45E−28 Cmah 2.64E−32 0.251319774 0.619 0.465 6.55E−28 Atf3 1.25E−31 0.262281273 0.327 0.179 3.11E−27 Baat 5.96E−31 −0.265815179 0.705 0.767 1.48E−26 Rpl36al 1.38E−30 −0.331844566 0.407 0.551 3.44E−26 Hebp1 1.59E−30 −0.274169133 0.663 0.75 3.96E−26 Aldh1b1 5.04E−30 0.360480753 0.255 0.132 1.25E−25 Insig2 1.14E−29 −0.275363349 0.75 0.81 2.82E−25 Efna1 1.15E−29 0.268455179 0.451 0.309 2.85E−25 Gadd45b 1.76E−29 −0.301158726 0.147 0.291 4.38E−25 G0s2 2.10E−29 −0.269113384 0.183 0.33 5.23E−25 Fdps 3.09E−28 −0.254137438 0.293 0.445 7.67E−24 Aqp8 1.90E−27 −0.273149234 0.366 0.505 4.72E−23 Ssr4 3.10E−27 −0.283161199 0.597 0.687 7.71E−23 Minos1 3.22E−27 −0.308403636 0.493 0.595 8.00E−23 Ndufa2 3.89E−27 −0.308306345 0.651 0.738 9.67E−23 Tmem243 8.31E−27 −0.275109242 0.436 0.557 2.06E−22 Rps21 1.13E−26 −0.316866281 0.451 0.579 2.81E−22 Ndufa5 1.69E−26 −0.310280044 0.451 0.567 4.19E−22 Tubb2a 2.11E−26 −0.260491764 0.297 0.431 5.24E−22 Akr1c14 4.84E−26 −0.280169437 0.63 0.707 1.20E−21 Atp5o 9.05E−26 −0.268645357 0.58 0.712 2.25E−21 Ppp2r5a 1.31E−25 −0.281895906 0.485 0.594 3.25E−21 Clpx 1.50E−25 −0.250587235 0.732 0.783 3.74E−21 Psmb1 2.29E−25 −0.271574562 0.716 0.759 5.68E−21 Rps9 2.57E−25 −0.30861002 0.554 0.675 6.38E−21 Nme1 3.82E−25 −0.291609359 0.531 0.622 9.48E−21 Ndufb5 5.36E−25 −0.274484363 0.516 0.612 1.33E−20 Rgn 1.09E−24 0.261094268 0.911 0.874 2.71E−20 Psma6 1.13E−24 −0.281709731 0.596 0.675 2.82E−20 Egr1 1.35E−24 0.271667356 0.565 0.447 3.36E−20 Rplp1 2.78E−24 −0.274821325 0.667 0.757 6.89E−20 Fam162a 4.60E−24 −0.280519821 0.41 0.53 1.14E−19 Rabac1 5.66E−24 −0.275369587 0.403 0.524 1.41E−19 4931406C07Rik 1.25E−23 −0.28178071 0.671 0.748 3.10E−19 Sc5d 1.59E−23 −0.274286355 0.779 0.776 3.96E−19 Bnip3 5.74E−23 −0.272700001 0.43 0.55 1.43E−18 Timm13 5.78E−23 −0.266267617 0.567 0.671 1.44E−18 Ndufs4 9.09E−23 −0.299960018 0.476 0.562 2.26E−18 Selk 1.84E−22 −0.279248941 0.378 0.486 4.58E−18 Ifi27 2.17E−22 0.274586258 0.565 0.453 5.38E−18 Cyp1a2 3.26E−22 −0.284567418 0.726 0.794 8.09E−18 Mrps18c 4.36E−22 −0.27427115 0.273 0.394 1.08E−17 Rpl13 1.42E−21 −0.282418264 0.349 0.464 3.52E−17 Rps8 1.02E−20 −0.279845708 0.36 0.471 2.52E−16 Sco2 1.24E−20 −0.250104753 0.389 0.508 3.07E−16 Rps15 1.38E−20 −0.324542895 0.435 0.528 3.43E−16 Nlrp12 4.33E−20 −0.269307598 0.314 0.43 1.08E−15 Timm8b 9.75E−20 −0.25098905 0.42 0.525 2.42E−15 Slc22a30 9.94E−20 −0.25736876 0.397 0.493 2.47E−15 Dhrs4 2.40E−19 −0.268862728 0.604 0.69 5.96E−15 Rps10 1.55E−17 −0.252659935 0.348 0.453 3.85E−13 Rpl34 5.76E−17 −0.264586248 0.299 0.398 1.43E−12 Hspe1 1.26E−16 −0.257910168 0.467 0.557 3.13E−12 Ftl1 1.88E−15 −0.347806606 0.328 0.409 4.66E−11 Usmg5 4.44E−15 −0.28365494 0.346 0.43 1.10E−10 Cebpb 1.24E−14 −0.267669957 0.38 0.45 3.07E−10 Gulo 1.57E−14 0.282891961 0.573 0.497 3.90E−10 Rpl26 5.46E−14 −0.264487941 0.463 0.53 1.36E−09 Rps19 2.07E−10 −0.25849266 0.409 0.474 5.15E−06 Cyp2e1 2.79E−10 0.296899706 0.88 0.911 6.94E−06 Glul 1.05E−08 0.495360357 0.25 0.18       0.000261488 Slc1a2 2.46E−07 0.262926395 0.078 0.042       0.006115724

To identify what cellular programs activate in response to each injury model, clustering and differential expression was performed over APAP and UT clusters and PH and UT clusters. Upregulation of genes unique to each injury model were identified, such as Gclc, a rate limiting enzyme in the synthesis of the anti-oxidant glutathione for APAP.

Tables 8A and 8B provide Composite DEG for partial hepatectomy (PH) and acetaminophen (APAP) treatment. DEG for each individual treatment condition pooled across all time points within PH conditions and all time points within APAP conditions to generate a composite list of all genes which are differentially expressed at any time point relative to untreated for each injury type.

Table 8C shows differentially expressed genes between APAP and PH treatment, with Table 9 providing pathway enrichments unique to APAP and Table 10 the pathway enrichments unique to PH.

TABLE 8A Differentially expressed genes between treatment (APAP and UT). ID A6logFC A24logFC A48logFC A6p A24p Mup17 −2.354358557  −1.800348604  −2.09635042   1.37E−209 0 Mup6 −1.871852037  −1.678184828  −2.032084932   2.16E−149  1.18E−255 Mup9 −2.004163996  −1.847446915  −1.93588422   9.10E−177 0 Mup19 −2.396345291  −1.699352699  −1.730868177   4.33E−227 0 Mup11 −3.213953203  −1.611434806  −1.621134615   1.04E−235 0 Mup18 −1.627956781  −1.727178347  −1.590870011   4.19E−157 0 Selenbp2 −1.009165718  −0.383324562  −1.190221952   6.93E−118 5.26E−63 Mup7 −0.941370494  NA −1.115587848  1.78E−67 NA Mup16 −1.602085539  −1.018975936  −1.100681479   1.22E−168  2.06E−200 mt-Co1 NA −1.43342755  −1.043307563  NA 0 Mup21 0.827249928 −0.697735774  −1.008171912  2.40E−75  2.15E−121 mt-Nd4 0.638848134 −1.957424825  −0.936405909  7.92E−71 0 mt-Nd2 NA −1.241926048  −0.898054789  NA 0 mt-Cytb NA −1.571232911  −0.8545555    NA 0 mt-Nd5 NA −1.383591054  −0.799147191  NA 0 Serpina1e −0.268413792  −0.284344569  −0.662045945  1.97E−26 8.67E−65 mt-Nd1 −0.388336084  −1.419683574  −0.591646758  2.80E−49 0 Mup3 −0.703483173  −0.806219448  −0.379596014   1.31E−157 0 Apoe −0.368966531  −0.421271729  0.407256897 3.19E−71  3.30E−238 Ces1c NA −0.278292823  0.466837177 NA 1.32E−78 Hmgcs2 NA −0.317281221  0.629289122 NA 1.04E−73 Angptl3 NA NA 0.7089371  NA NA Ang −0.662883759  NA 0.7089371  5.46E−47 NA Chchd10 −0.40191686  NA 0.720691838 2.84E−29 NA Chchd1 −0.439819068  NA 0.720691838 4.34E−20 NA Mat1a 0.790765268 NA 1.000433202  3.26E−113 NA Cyp4a10 0.456645767 −0.742207081  1.135370857 1.93E−12 2.66E−98 Cyp4a14 1.122498795 −0.372863761  1.704093543 2.33E−95 6.77E−27 Hbb-bs 2.862044849 1.042581651 NA 0       2.58E−59 Hmox1 1.347585217 NA NA 0       NA Gm26924 1.16085221  1.419027502 NA  3.70E−144 0 Fga 0.69335023  0.828543313 NA  2.44E−115 0 n-R5-8s1 0.766100662 1.252818829 NA  1.81E−109 0 Fgg 0.615329068 0.680530925 NA  1.29E−106 0 Fgb 0.646934246 0.744973762 NA  4.40E−105 0 Grip2 NA 0.877868293 NA NA 0 Apoa2 −0.542784959  −0.545518454  NA  6.54E−122 0 Apoh −0.262314298  NA 0.411790107 4.51E−22 NA Ttpa NA NA 0.601240096 NA NA Lars2 1.391744455 1.711400221 NA  9.69E−109  1.38E−293 Gm13775 −1.065618856  −1.032451941  −1.07808822  3.12E−88  3.97E−187 Cdo1 NA NA 0.517045053 NA NA Gm15564 1.443066465 1.820580657 NA  4.17E−104  6.31E−292 S100a9 1.342849617 NA NA  5.31E−281 NA Tnfrsf12a 1.117506296 NA NA  5.70E−279 NA Gm24601 0.46836359  0.984391691 NA  4.45E−106  2.17E−275 Apoc2 NA NA 0.782126085 NA NA Retsat 0.491096059 −0.365840188  0.681307283 4.57E−36 3.00E−43 Ttr −0.530625643  NA 0.388907438  3.44E−101 NA Sephs2 NA 0.889992859 NA NA  2.83E−263 S100a8 1.127879209 NA NA  1.92E−258 NA Nudt7 −1.564266936  NA −1.14157535   1.44E−129 NA mt-Rnr2 NA −0.778341998  −0.559446336  NA  5.04E−251 Ppl 0.879840886 NA NA  9.97E−249 NA Serpina1a −0.378457074  −0.675201963  NA 8.08E−39  4.32E−247 Acaa1b −0.732823459  −0.85084133  NA 9.23E−93  4.51E−247 Sepp1 NA 0.448586822 0.33970689  NA  1.35E−231 Srxn1 1.878352012 NA NA  2.22E−243 NA Apoc1 −0.871282735  −0.380336769  0.392095407  1.40E−171  2.01E−117 Mup5 −1.23728834  −1.370621307  −1.351810718  1.04E−61  6.49E−171 Fgl1 NA 0.864933885 NA NA  1.60E−238 Gpx1 −0.768556331  −0.50797139  NA  9.80E−161  6.77E−238 Mt2 2.06273693  NA NA  1.90E−237 NA Ankrd55 −1.250834631  −1.8735659    −0.974280427  1.82E−54  4.38E−235 Mup15 −1.316464146  −1.234928375  −1.26121256  1.10E−84  1.08E−153 Mfsd2a 0.666142747 NA 0.612232714 7.88E−65 NA Mt1 2.387707773 −0.348193009  0.356326784  3.51E−232 3.61E−18 Ndrg2 NA NA 0.41219937  NA NA Ahsg NA NA 0.292489576 NA NA Hrg NA NA 0.518895355 NA NA mt-Co2 −1.105332856  −1.396543228  −0.918784455  3.38E−58  7.79E−219 Sult1a1 0.318989978 NA 0.560453494 6.64E−07 NA Agt NA NA 0.520454244 NA NA Cyb5 −0.71018958  −0.704808492  NA 7.09E−94  8.36E−212 Fth1 NA NA 0.378367166 NA NA Snord118 NA 0.391412496 0.617425052 NA 4.02E−38 Fabp1 −1.016174848  NA NA  1.10E−198 NA Slco1a4 0.313739505 NA 0.552641329 4.36E−10 NA mt-Rnr1 NA −0.456211361  −0.485399855  NA  2.01E−123 Saa1 NA 0.558211954 −1.078220383  NA 9.12E−37 Hilpda 0.778625914 NA NA  3.64E−193 NA Gclc 1.902837282 NA NA  1.67E−192 NA Cp 0.254076812 0.317404056 0.436243259 2.41E−10 1.74E−45 Igfbp4 NA NA 0.43528879  NA NA Akr1c6 −1.586259995  −0.317638782  −0.468988487   2.54E−187 2.86E−52 Rbp4 NA NA 0.301440617 NA NA Mup12 −1.269973728  NA −0.767698995   4.63E−127 NA Serpina1d −0.289011223  −0.494007182  NA 2.07E−26  1.74E−184 Hspa5 0.268221373 0.610549064 0.291184144 9.35E−08  9.07E−184 Mgst1 −1.060154854  NA NA  2.13E−181 NA Rdh7 −0.418625957  −0.269043262  0.364161562 7.41E−48 1.69E−54 Apoc3 −0.768781074  −0.440433124  0.327008256  1.59E−133  3.26E−151 Herpud1 −0.497586072  NA 0.513571228 1.98E−36 NA Aldob 0.315339576 NA 0.365460648 1.58E−35 NA Abcd2 NA NA 0.285090597 NA NA Gc NA NA 0.259816642 NA NA Abcb4 NA NA 0.494736917 NA NA mt-Co3 −0.705930608  −1.167027737  −0.915108473  1.72E−25  9.57E−168 Ugt2b5 −0.603351248  −0.576498765  NA 3.90E−81  9.60E−175 Slc27a2 NA NA 0.385256962 NA NA Ccl6 0.78914235  NA NA  1.24E−171 NA St3gal5 0.607639775 NA 0.542378437 6.13E−38 NA Hbb-bt 1.430134393 0.364374989 NA  2.56E−170 3.52E−29 Reep6 NA NA 0.514272451 NA NA Slc16a6 0.911357108 NA NA  4.06E−168 NA Ttc36 −0.660645659  NA 0.38128834  8.42E−81 NA Adh1 −1.255028206  −0.342018972  NA  1.90E−167 8.71E−80 Gsta3 −0.806290466  −0.66935487  NA 6.16E−95  2.44E−166 Cvp2e1 −2.318570161  −0.499033632  NA  4.79E−166 3.18E−51 Plin2 1.461295758 NA NA  8.58E−163 NA Il1r1 1.244999819 NA NA  1.47E−162 NA F2 NA NA 0.32133198  NA NA Decr1 NA NA 0.466364339 NA NA Actb 1.059835055 0.38446276  −0.294140078   6.06E−159 5.37E−69 Slc25a47 0.428932953 NA 0.502661475 2.18E−12 NA Srgn 0.934067453 NA NA  5.07E−158 NA Pabpc1 0.410051805 NA 0.494914201 4.92E−19 NA Cyp2d9 −0.640698605  −0.567166215  NA 2.15E−73  3.96E−157 Hyou1 NA 0.846484822 NA NA  1.62E−156 Lcat NA NA 0.436082968 NA NA Grn 0.540768685 NA 0.473252349 1.38E−25 NA Hsd3b5 −1.069520224  NA −0.830145941  2.04E−80 NA Ube2r2 NA NA 0.46659877  NA NA Hamp −1.02112368  −0.826148443  NA 2.14E−94  2.59E−153 Apoa5 NA −0.298987336  0.323188383 NA 3.48E−59 Cdkn1a 1.2152557  NA NA  2.99E−152 NA Serpina1c NA −0.402626732  NA NA  7.17E−151 Gstp1 −0.264374672  −0.430197368  −0.855831436  0.00132565  1.39E−27 Tubb6 0.576687679 NA NA  6.13E−150 NA Apoc4 −1.002265767  −0.428496936  NA  9.54E−150  3.56E−114 Nid1 0.342599117 NA NA  1.04E−149 NA Calr NA 0.555145472 NA NA  1.67E−148 Klf6 0.732407935 NA NA  1.50E−147 NA Cers6 0.532818648 NA NA  8.16E−146 NA Hmgcl NA NA 0.473794522 NA NA Aldh9a1 NA NA 0.415934269 NA NA Txnrd1 1.443578942 0.260866185 NA  1.43E−144 1.44E−15 Il1b 0.742893545 NA NA  1.02E−143 NA Hspa8 NA −0.359978165  0.420379148 NA 1.12E−41 Psat1 0.301248562 NA NA  8.43E−143 NA Gm23935 0.424222263 0.721300311 0.50194422  1       0.068577969 Tmbim6 −0.271070995  NA 0.338652766 2.03E−15 NA Rgn −1.573093006  NA NA  9.97E−141 NA Amy1 −0.282967905  NA 0.432738347 2.05E−09 NA Uqcrq −0.88665513  −0.595921048  NA  4.23E−106  1.50E−140 Scd1 −0.466125013  0.726687286 0.519218079 5.04E−19  2.08E−139 Itih4 NA 0.525074867 NA NA  4.26E−137 Gyk 0.368418571 NA 0.402444184 5.71E−07 NA Hp NA 0.431328341 NA NA  8.95E−137 Chka 1.375010255 NA NA  2.35E−136 NA Pdia3 NA 0.593769188 NA NA  7.36E−136 Decr2 NA NA 0.418851877 NA NA Cyp3a25 −0.386094858  NA 0.318573266 1.37E−27 NA Serping1 NA NA 0.41280952  NA NA Wbp1l 0.553507326 NA 0.440462928 2.48E−26 NA Hsp90b1 −0.261479921  0.534208217 NA 2.81E−10  6.37E−134 Gnmt −0.33340449  −0.46036106  NA 1.40E−31  1.33E−133 Atp5k −0.47725773  NA 0.408878378 2.10E−29 NA 2010003K11Rik 0.588354735 NA NA  2.61E−131 NA Serpina3m 0.967441963 NA 0.432583404 2.50E−94 NA Slco1b2 −1.087378176  NA 0.386023002  3.68E−129 NA Lipa NA NA 0.41833763  NA NA Mup20 NA −0.281871664  −0.476207303  NA 9.36E−26 Rgs16 NA NA 0.322559157 NA NA Bhmt −0.311413339  −0.520184894  NA 5.24E−16  1.20E−127 Vtn NA NA 0.333811366 NA NA Plin5 0.296281512 −0.277759837  0.352087102 6.88E−09 2.38E−16 C3 0.44276078  0.449521065 0.259166718 1.55E−58  1.23E−125 Agpat6 NA NA 0.396260224 NA NA Acat1 NA NA 0.368871999 NA NA Ets2 0.695623802 NA NA  2.30E−125 NA Mup4 −0.99530818  −1.087038527  −0.953101828  1.26E−43  1.96E−121 Atp5h −0.6398091    −0.579498914  0.434163543 8.64E−40 7.16E−69 Car3 −1.036093133  NA −0.405308591   1.61E−124 NA Acbd5 −0.3952179    NA 0.385608793 2.30E−17 NA Nr1i3 −0.412654588  −0.282083592  0.425883248 1.00E−16 1.07E−16 Crat NA NA 0.255626614 NA NA Slc27a5 NA NA 0.336994904 NA NA Oaf −0.7328674    NA 0.403567608 4.77E−65 NA Cyp3a11 −0.423130745  −0.363891177  0.313927334 1.90E−61  1.05E−122 Krt18 1.257881489 NA NA  3.97E−121 NA Elovl3 −0.506724135  −0.675967012  −0.442652848  4.74E−35  6.30E−121 Cox5a NA NA 0.40236048  NA NA Ahcy NA −0.562968597  NA NA  6.43E−120 Sdhc NA NA 0.394392518 NA NA Gstt3 NA NA 0.350739865 NA NA Asl 0.558638879 NA 0.438458339 8.13E−37 NA Atp5b NA NA 0.291727476 NA NA C9 −0.395507776  NA −0.427055258  5.97E−29 NA Cyp2b10 −0.517460658  −1.164490931  NA 2.09E−08  9.40E−117 1100001G20Rik −0.851607217  NA NA  1.14E−116 NA Slc25a20 NA NA 0.380017899 NA NA Hba-a1 0.734957385 NA NA  2.58E−115 NA Ildr2 NA NA 0.267607713 NA NA Ppara −0.287133273  NA 0.35885744  1.36E−08 NA Dusp5 0.296374788 NA NA  1.01E−114 NA Mup8 −0.752577709  −0.613334367  −0.79575704  2.07E−27 4.14E−25 P4hb NA 0.405223744 0.250660872 NA  2.27E−113 2810007J24Rik −0.914301122  NA NA  6.76E−113 NA Rpl38 NA NA 0.254329206 NA NA Tgoln1 0.265747623 NA 0.38833408  9.27E−05 NA Cox4i1 −0.515989169  −0.454243631  NA 5.83E−60  4.62E−112 Brap NA NA 0.349229859 NA NA Cox8a −0.399332537  NA 0.44171223  1.73E−19 NA Bfar NA NA 0.290332897 NA NA D17Wsu92e 0.252482331 NA 0.371951808 0.259418286 NA Glud1 NA 0.451048591 NA NA  6.55E−110 Slc40a1 0.466969696 NA 0.356026755 6.46E−08 NA Ephx2 NA −0.369303553  0.281258562 NA 3.71E−68 Bnip3 −0.336168189  −0.292803703  0.403206563 1.17E−13 2.86E−22 Rnase4 −1.049196753  0.517836403 NA  1.89E−107 3.56E−82 Dhcr24 NA 0.423756767 0.387274317 NA 3.44E−48 Myh9 1.160233135 0.6391137  NA  3.10E−107 2.47E−87 Acad11 NA NA 0.357135026 NA NA Fn1 0.521230804 0.699634526 0.292522175 2.99E−26  1.87E−106 Mia3 NA NA 0.364623797 NA NA Gm6484 NA NA 0.304268201 NA NA Zfp91 NA NA 0.370686172 NA NA Gm2a NA NA 0.383109253 NA NA Sec14l2 −0.789737513  NA 0.321333578 5.48E−79 NA Cyp2a12 NA NA 0.374332361 NA NA Krt8 1.195874806 NA NA  1.04E−103 NA Lpin2 0.686687426 0.277576437 0.385908326 6.95E−36 6.61E−21 Clec4f 1.108180782 NA NA  2.17E−103 NA Cidec 0.299384206 NA NA  1.71E−102 NA B2m −0.330354919  −0.417973886  NA 5.62E−26  1.86E−102 Slc4a4 0.420259653 NA 0.331670131 8.17E−17 NA Sh3glb1 NA NA 0.326006747 NA NA Tmed5 0.401633325 NA 0.345007803 1.17E−13 NA Serpinf1 NA NA 0.319550979 NA NA 0610005C13Rik −0.425135941  NA 0.34237016  1.47E−21 NA Rpl4 NA NA 0.283935593 NA NA Dbi 0.716365271 NA NA  3.56E−101 NA Apoa4 1.367998503 NA 0.495579268  8.56E−101 NA Acot12 NA NA 0.307840041 NA NA Acot1 −0.288638646  −0.286204152  0.307840041 3.05E−10 5.23E−33 Scp2 −0.519124916  NA −0.325161752  1.05E−60 NA Uroc1 NA NA 0.416226092 NA NA Bcl2l1 0.775118224 NA NA 1.02E−99 NA Mmp8 0.359005863 NA NA 1.02E−99 NA Cyp2c29 −1.149629979  −0.586003377  NA 1.97E−99 2.74E−69 Snord13 NA NA 0.261078586 NA NA Acadl NA NA 0.316216015 NA NA Cpt1a 0.261119591 NA 0.372935212 0.000289401 NA Akr1d1 −0.278865899  NA 0.361037667 6.11E−10 NA Cyp7b1 −0.65802273  NA −0.542403458  4.96E−47 NA Mgll NA NA 0.333899751 NA NA Sult1d1 −0.316458159  NA 0.45987026  4.92E−13 NA Slc25a10 −0.282805644  NA 0.343272504 4.64E−10 NA Vnn3 NA NA 0.276458974 NA NA Pigr 0.348711695 NA 0.386842112 8.87E−26 NA Pzp NA 0.41600896  NA NA 3.34E−97 Serpina1b NA −0.301770579  NA NA 4.66E−97 Tmem205 −0.774742732  −0.472107677  NA 1.21E−96 1.05E−96 Mup14 −0.697469805  NA −0.760766854  2.00E−25 NA Ces1b NA NA 0.372958858 NA NA C8g −0.654510262  −0.481964476  NA 3.81E−68 4.13E−96 Cd14 0.362089625 NA NA 2.79E−95 NA Mtdh NA NA 0.30466184  NA NA Hdlbp 0.345721467 0.565147241 NA 5.40E−08 5.10E−95 Tmbim4 NA NA 0.32269634  NA NA Saa2 0.558658405 0.964488054 −0.390082382  0.000262015 8.96E−95 Abcc3 NA NA 0.363799323 NA NA Serpina10 NA 0.565046404 NA NA 8.21E−94 Cyp2c44 −0.372953076  NA 0.385935584 6.35E−18 NA Rcan1 0.707283787 NA NA 1.24E−93 NA Arrdc3 NA 0.526871989 NA NA 2.74E−93 Hsd3b7 −1.0059958    −0.395256634  −0.382738321  3.79E−93 2.93E−47 Rell1 0.591181865 NA NA 1.02E−92 NA Prdx1 −0.529229113  −0.267665106  −0.361890861  7.29E−52 1.94E−38 Fah −0.259255187  NA 0.302494707 1.82E−10 NA Chpt1 NA NA 0.35662056  NA NA Mthfd2 0.262448025 NA NA 1.46E−92 NA Gfra1 0.386382804 NA 0.320843264 8.44E−11 NA Retnlg 0.375148336 NA NA 4.49E−92 NA Pbld1 −0.442542986  NA 0.322688203 7.81E−24 NA Creld2 NA 0.608652695 NA NA 1.18E−91 Aplp2 NA NA 0.33938781  NA NA Lifr −0.626180925  NA −0.563681141  5.39E−42 NA Ces1d NA −0.428906017  0.285254637 NA 8.07E−91 D10Wsu102e 0.58780186  NA NA 2.09E−90 NA Camk2n1 NA NA 0.250109512 NA NA Rps27l −0.865927484  −0.548506218  NA 1.39E−81 5.43E−90 Bche NA NA 0.313419985 NA NA Itih3 0.546240791 0.492908293 NA 1.40E−47 1.11E−89 Plscr1 0.444489505 NA NA 2.65E−89 NA Gm24270 NA 0.26796863  NA NA 3.13E−89 Tmem56 0.273557142 NA 0.335238196 1       NA Rdx NA 0.373557306 0.318521875 NA 1.28E−35 Abca6 NA NA 0.33284944  NA NA Gpld1 NA NA 0.328106789 NA NA Lrrc58 1.001096085 NA NA 3.66E−88 NA Hba-a2 0.553546734 NA NA 5.15E−88 NA Fxyd5 0.274279595 NA NA 7.76E−88 NA Cyp8b1 −0.889229825  −0.553616206  0.282315072 6.32E−84 8.76E−88 Cox6a1 −0.48722865  −0.366697192  0.292128773 1.69E−41 9.18E−60 Ctage5 NA NA 0.328678207 NA NA Pex11a NA NA 0.350827626 NA NA Ass1 NA NA −0.314400604  NA NA Mttp NA NA 0.311504107 NA NA Eci2 NA NA 0.311004843 NA NA Prodh2 NA NA 0.345294809 NA NA Gadd45g −0.355407686  −0.614019025  NA 3.32E−18 7.38E−86 Psen2 −0.947373772  NA NA 1.77E−85 NA Creg1 NA NA 0.276773054 NA NA BC025446 NA 0.29422883  0.272610935 NA 6.33E−31 Serpina3n 0.848313239 0.413696164 0.346482791 4.98E−61 4.35E−45 Slc10a1 −0.325757408  NA 0.314325805 3.37E−14 NA Met NA 0.288332662 0.283916114 NA 8.49E−25 Mettl7b −0.452656656  NA 0.283916114 2.76E−30 NA Pck1 −0.652190949  NA 0.271859881 1.90E−84 NA Oat −1.224853019  −0.521209343  NA 6.25E−84 1.40E−70 Pcbp2 NA NA 0.310347013 NA NA Atf5 NA NA 0.329004772 NA NA Tyrobp 0.466551501 NA NA 1.85E−83 NA C230081A13Rik 0.426976229 NA NA 3.42E−83 NA Hnf4a 0.879108718 0.454905579 0.314710574 6.36E−71 9.91E−71 Atxn7l3b NA NA 0.306239775 NA NA G0s2 NA NA 0.346452213 NA NA F10 −0.271936054  NA 0.279095541 3.10E−11 NA Pla2g7 0.282344956 NA NA 9.47E−83 NA Rplp0 NA NA −0.430901519  NA NA Gcdh −0.300320098  NA 0.273385895 7.95E−15 NA Creb3l3 NA NA 0.275700825 NA NA Ssr3 NA 0.521769281 NA NA 5.71E−82 Eef1a1 0.282586942 0.439251983 NA 1.02E−09 2.20E−81 Slc39a14 1.012749203 0.323040019 NA 2.25E−81 8.94E−22 Man2a1 0.497115325 0.28327895  0.332755834 6.13E−22 2.79E−19 Cox6c −0.844280539  −0.502802751  NA 3.24E−81 2.39E−77 Il1r2 0.323447978 NA NA 5.62E−81 NA Actn4 0.312388865 NA 0.299765947 1.98E−06 NA Ptprc 0.416505491 NA NA 1.46E−80 NA Eif5 0.576301866 NA 0.284340466 6.87E−46 NA Slc25a13 NA NA 0.285473174 NA NA Hint1 −0.673880575  −0.473665273  NA 4.75E−61 1.71E−80 Echs1 −0.331606352  NA 0.318692311 4.24E−19 NA Aco2 NA NA 0.285855791 NA NA Pnpla8 NA NA 0.295631611 NA NA C1qb 0.681679654 NA NA 1.02E−79 NA Hsd17b10 0.377206484 NA 0.361579378 4.44E−19 NA Egfr NA 0.504957782 0.473388687 NA 1.72E−79 Cyp2a5 −1.498910166  −0.681077987  NA 3.74E−79 3.04E−57 Asgr2 NA NA 0.306445529 NA NA Tmsb4x 0.780616209 NA NA 7.99E−79 NA Hsd17b13 0.680828119 NA 0.550399594 1.17E−50 NA Dennd5b NA 0.293458876 0.266493539 NA 1.07E−18 Ctsh NA NA 0.32445036  NA NA Igf1 NA NA 0.295791825 NA NA Apc 0.27896726  0.606730845 NA 7.91E−19 2.16E−78 Apcs 0.298925674 0.606730845 NA 0.75840106  2.16E−78 Ctss 0.764167083 NA NA 2.26E−78 NA Cyp2d26 NA NA 0.259136874 NA NA Tcea3 −0.355007815  NA 0.3163181  1.20E−14 NA Klf9 NA NA 0.293415875 NA NA Orm1 NA 0.365144434 −0.31003929  NA 4.87E−78 Clec4d 0.26359638  NA NA 5.98E−78 NA Mlycd −0.290948387  NA 0.313046697 3.48E−09 NA Maob NA NA 0.32037326  NA NA Kif1b 0.371764707 NA 0.299610278 0.000173425 NA Insig2 0.669991504 NA 0.300825179 1.24E−48 NA Ces3a −0.52533635  −0.36873562  NA 1.00E−62 5.80E−77 G6pc −0.960058274  NA NA 1.00E−76 NA Cth NA −0.510899065  NA NA 1.34E−76 Pgrmc1 NA 0.350152674 NA NA 1.59E−76 Ugt2b1 −0.776816931  −0.289461704  NA 2.28E−76 4.20E−34 Mup13 −0.77574306  −0.694889672  −0.55255936  8.39E−43 2.45E−76 Gabarap −0.442546824  NA 0.289400057 2.22E−27 NA Arhgap5 0.264043476 0.295235575 0.288514066 0.057064443 2.61E−16 Cyp1a2 −0.993935836  NA −0.445766232  1.08E−75 NA Hgd −0.758572265  NA NA 1.96E−75 NA Adck3 −0.87611538  −0.28251534  NA 2.27E−75 6.63E−24 Abhd14b −0.39366782  NA 0.299363281 4.62E−20 NA Serinc3 0.35928911  NA 0.292320724 1.17E−06 NA Gltscr2 NA NA 0.255310647 NA NA Vcam1 0.457401491 NA NA 6.00E−75 NA Urah −0.764109132  NA NA 1.55E−74 NA Sord −0.383628337  NA 0.26850985  4.92E−29 NA Agpat9 0.327040595 NA NA 2.14E−74 NA Etnppl 0.41816318  −0.428291487  0.496712405 2.26E−13 4.23E−36 Por 0.335963246 −0.271635533  0.33194923  4.49E−09 2.42E−08 Rsp14 −0.402093042  −0.292251029  −0.348405505  1.50E−30 3.26E−44 Lamp1 NA NA 0.268283663 NA NA Plek 0.308857869 NA NA 1.40E−73 NA Ctsa NA NA 0.252009224 NA NA Mrap 0.884099926 NA NA 2.65E−73 NA Dnajc3 NA 0.45638751  NA NA 2.66E−73 Adamts1 0.282556845 NA NA 8.88E−73 NA Hadh NA NA 0.288772268 NA NA C8b −0.315917765  0.318703124 −0.360171247  1.33E−15 1.74E−50 Csad −0.559786018  −0.531252493  NA 1.25E−34 1.92E−72 Nr1d2 NA 0.430636791 NA NA 2.60E−72 Sod1 −0.439319795  −0.303629074  NA 7.55E−60 3.30E−72 Ech1 NA −0.429132615  0.250481301 NA 5.62E−72 Ddb1 NA NA 0.277809186 NA NA Kng1 NA 0.265777676 NA NA 1.32E−71 Shmt1 −0.393237106  NA 0.278820727 1.10E−18 NA Acsl1 −0.343424014  −0.370316988  0.256335416 2.16E−20 1.40E−54 C4b NA NA 0.283273876 NA NA Gcnt2 0.537509676 NA NA 4.50E−70 NA Csf1r 0.704458586 NA NA 4.70E−70 NA Ggnbp2 NA NA 0.272604502 NA NA Nfe2l1 NA NA 0.27034473  NA NA Tomm70a NA 0.268786029 0.265762726 NA 3.18E−17 Steap4 0.437231109 0.475973731 NA 3.54E−11 6.59E−69 Atp2a2 0.494962728 NA 0.305636215 2.90E−18 NA Cd1d1 NA NA 0.291156805 NA NA Comt −0.368377448  NA −0.286248465  2.17E−28 NA Sec62 NA NA 0.251575572 NA NA Cxcr2 0.40229963  NA NA 2.86E−68 NA Slc7a2 NA 0.352564931 0.34497807  NA 1.75E−31 C130074G19Rik −0.356338948  NA 0.250322698 8.18E−13 NA Apob 0.580156235 0.4272457  NA 5.69E−61 4.36E−68 Furin 0.253587917 NA 0.278163716 0.405633752 NA Cxcl1 0.370070418 0.449766784 0.257250112 4.89E−08 1.26E−30 Cxcl12 −0.305838679  NA 0.257250112 6.12E−10 NA Khk −0.491453217  −0.29761703  0.310103866 3.36E−37 4.03E−35 Ei24 NA NA 0.257327011 NA NA Cd163 0.440845529 NA NA 1.51E−67 NA Trp53inp1 1.008414088 0.367960906 NA 1.52E−67 2.95E−29 Eif4g2 0.559692663 0.465990267 NA 5.94E−33 1.62E−67 Gys2 NA NA 0.274401611 NA NA Dmgdh NA NA 0.265846058 NA NA Tob1 −0.338705886  0.312925608 0.284985634 9.48E−15 1.91E−21 Ubc −0.661839716  −0.370487607  NA 4.04E−67 2.42E−49 Cbr1 0.284717454 NA 0.260731659 7.95E−05 NA Pon1 −0.685751275  −0.322748466  NA 1.66E−66 5.87E−44 Suds3 NA NA 0.25388963  NA NA 1700017B05Rik 0.330656885 NA NA 2.40E−66 NA Ugp2 NA NA 0.297335445 NA NA Iigp1 0.768753667 0.454178892 NA 2.65E−29 7.59E−66 Nop58 0.663449653 NA NA 2.13E−65 NA Padi3 0.295682522 NA NA 2.63E−65 NA Pipox NA NA 0.272543042 NA NA Ndufa4 −0.683126695  −0.443311137  NA 1.11E−61 3.70E−65 Gsta1 0.407606856 NA NA 7.64E−65 NA F9 NA NA 0.256805166 NA NA B4galt5 0.476306558 NA NA 1.12E−64 NA F12 NA NA 0.256737037 NA NA Fcgrt NA −0.269314211  0.258478842 NA 8.21E−19 Fmo5 0.286219883 NA 0.252070931 1.05E−08 NA Rnf144a 0.313046134 NA NA 7.90E−64 NA Ugt2b36 −0.583431487  −0.329316239  NA 1.36E−63 1.07E−57 Sardh NA NA 0.269183147 NA NA Iqgap1 0.45544473  NA NA 1.82E−63 NA Creb3l2 0.427180051 NA NA 1.91E−63 NA Slc22a1 −0.797941816  NA NA 2.27E−63 NA Lyz2 0.732183369 NA NA 2.49E−63 NA Bach1 0.832333098 NA NA 2.51E−63 NA Lpgat1 0.595219291 0.394625955 0.257600415 4.45E−21 3.86E−28 Atp1a1 0.419079339 0.270031448 0.262770413 2.42E−07 1.97E−06 Fam134b 0.893562894 NA NA 5.02E−63 NA Hsd17b4 NA NA 0.253232967 NA NA Gabarapl1 NA NA 0.260716513 NA NA Cd5l 0.693485826 NA NA 1.08E−62 NA Elovl2 NA 0.45224665  NA NA 1.22E−62 Lrg1 0.490792829 0.436838294 NA 1.92E−28 1.37E−62 Hgfac NA NA 0.252189991 NA NA Atp5d NA NA 0.250062798 NA NA Efhd2 0.583831769 NA NA 3.26E−62 NA Pcbd1 −0.687761883  NA NA 6.29E−62 NA mmu-mir-6240 1.101237189 NA NA 9.82E−62 NA Hagh −0.674009711  NA NA 1.62E−61 NA Hsd3b3 −0.779501123  NA −0.299662144  1.98E−61 NA Tmem106b 0.280204492 NA 0.270357032 0.106548775 NA Ctsd NA NA 0.257862212 NA NA Cd44 0.303745221 NA NA 5.24E−61 NA Rdh16 NA NA 0.269182372 NA NA Cyp2c70 −0.551134023  0.336400438 −0.395158527  4.62E−37 2.87E−40 Thrsp −0.724961807  NA −0.689057582  3.13E−30 NA Hadha NA NA 0.250937029 NA NA Sdhd −0.335261252  NA 0.320841923 2.07E−18 NA Mbl1 −0.713006005  NA NA 1.05E−60 NA Ddt −0.522221147  −0.422410948  NA 1.48E−41 1.33E−60 Eif1a 0.795281298 NA NA 1.80E−60 NA Alb 0.420298986 NA NA 1.86E−60 NA Pdia4 −0.27191836  0.488166898 NA 8.81E−08 1.94E−60 F5 NA NA 0.300566587 NA NA Laptm5 0.338180771 NA NA 3.31E−60 NA Slc2a2 −0.312348392  NA 0.272297971 2.36E−14 NA Sfxn1 NA NA 0.304885886 NA NA Epas1 0.775763153 NA NA 7.57E−60 NA Alas1 NA −0.489837477  NA NA 8.49E−60 Cd97 0.345774315 NA NA 1.02E−59 NA Hacl1 −0.706897734  NA NA 1.20E−59 NA Oaz1 −0.347228062  −0.374797984  −0.418528822  1.73E−17 8.14E−43 Hpd −0.518180386  −0.313324027  NA 2.47E−59 1.72E−56 Cd74 0.453937562 NA NA 3.15E−59 NA Aldh3a2 −0.834229334  −0.300776093  0.307877353 3.38E−59 3.40E−27 Gclm 0.269864161 NA 0.258765469 2.58E−05 NA Serpina3c −0.287011328  −0.408878947  −0.472511045  7.83E−06 1.55E−34 Sdc4 0.619597869 NA NA 9.47E−59 NA Ubxn4 NA NA 0.250313647 NA NA Ptms NA NA 0.267838974 NA NA Wfdc17 0.486653465 NA NA 2.57E−58 NA Gsta2 NA NA 0.252161786 NA NA 1110008F13Rik −0.37509166  −0.455270589  NA 2.46E−19 4.13E−58 Fkbp5 0.516128063 NA NA 1.44E−57 NA mt-Nd6 NA −0.477851134  NA NA 1.67E−57 Kctd3 0.260833465 NA NA 2.11E−57 NA Sec61a1 NA 0.313944633 0.263729835 NA 2.96E−24 Ddx21 0.73138069  NA NA 2.25E−57 NA Pdcd4 NA 0.48815423  NA NA 3.64E−57 Upb1 −0.418695518  NA 0.25038758  3.32E−25 NA Cyp2c37 −0.886903784  −0.487522606  NA 9.93E−57 9.75E−56 Cd53 0.265579528 NA NA 1.37E−56 NA Park7 −0.260230015  NA 0.251517689 5.75E−09 NA Hic2 0.289767391 NA NA 2.03E−56 NA Sat1 0.68869896  NA NA 2.31E−56 NA Btg2 0.832086378 NA NA 3.81E−56 NA Usmg5 −0.43049483  NA 0.278730923 2.85E−18 NA Rgs2 0.395729601 NA NA 7.50E−56 NA Chchd2 −0.552503492  −0.394916772  NA 2.39E−48 7.88E−56 Slc37a4 NA NA 0.268318739 NA NA Inmt −0.731016404  −0.44352952  −0.25322177  1.21E−55 1.57E−51 Cyp2d10 NA −0.323151441  NA NA 1.31E−55 Itgb2 0.272302012 NA NA 1.36E−55 NA Cps1 NA 0.32450205  NA NA 1.45E−55 Keg1 −0.824548137  NA −0.521611435  1.46E−55 NA C1qc 0.586092716 NA NA 2.05E−55 NA AI182371 −0.319894937  0.447854829 NA 9.02E−17 2.62E−55 Rock2 0.594094466 NA NA 2.90E−55 NA Sqstm1 0.743150456 NA NA 4.59E−55 NA Fndc3b 0.409645989 0.348474602 NA 1.32E−37 4.69E−55 Uox −0.553115511  NA NA 6.13E−55 NA Gulo −0.801665727  NA NA 6.80E−55 NA mt-Tq NA 0.287889985 NA NA 7.13E−55 C8a NA 0.333650228 −0.327131388  NA 3.84E−39 Tiparp 0.545567123 NA NA 8.73E−55 NA Fcgr3 0.308247077 NA NA 1.21E−54 NA Uqcr11 −0.603079991  −0.263241396  NA 1.37E−54 5.87E−27 Atp5e −0.650247857  −0.313641686  NA 2.15E−54 1.78E−29 Tram1 NA 0.411080257 NA NA 2.39E−54 Prg4 NA 0.430643187 NA NA 3.20E−54 Upp2 −0.69025963  NA NA 3.29E−54 NA H2-Ab1 0.460956687 NA NA 3.42E−54 NA Gm26917 0.60120474  0.823736053 NA 6.50E−24 5.26E−54 Aldh8a1 −0.683676902  NA NA 5.66E−54 NA Glyat −0.647687911  NA NA 1.11E−53 NA Msrb1 −0.59903268  NA NA 1.16E−53 NA Manf NA 0.468881688 NA NA 1.60E−53 Spred1 0.388422711 NA NA 1.65E−53 NA Orm2 NA 0.271460545 NA NA 2.71E−53 Sparcl1 −0.253616986  −0.253616986  −0.253616986  2.56E−11 1.01E−31 Cat NA 0.262624418 NA NA 7.22E−53 Ndufb11 −0.509671057  −0.42752525  −0.275645983  3.19E−34 8.28E−53 C1qa 0.514846404 NA NA 1.51E−52 NA Cldn14 0.364540783 NA NA 1.86E−52 NA Heatr1 0.406005371 NA NA 2.23E−52 NA Calm1 NA 0.413146039 NA NA 2.28E−52 Insig1 NA 0.465534816 NA NA 3.03E−52 Cfh NA 0.400919606 −0.306325678  NA 3.24E−52 Ppp2r5a −0.260504538  NA 0.250897706 9.42E−10 NA Hc NA 0.367935082 NA NA 1.11E−51 Hebp1 −0.635432267  NA NA 1.18E−51 NA Ces1e NA NA 0.265618893 NA NA Cox7b −0.642240776  −0.267397469  NA 3.42E−51 4.55E−23 Abhd2 0.484366625 NA NA 1.13E−50 NA Picalm 0.754529703 NA NA 1.39E−50 NA Igfbp1 1.058689301 −0.316195447  NA 1.68E−50 9.05E−32 Haao −0.591181029  NA NA 2.08E−50 NA Canx NA 0.343383207 NA NA 2.09E−50 Cebpb −0.361738286  −0.471579534  NA 9.79E−11 2.38E−50 Stat3 0.715400235 0.297428438 NA 2.74E−50 8.01E−18 Fgl2 0.281793883 NA NA 2.86E−50 NA AA474408 0.347079511 0.43640813  NA 8.58E−25 3.01E−50 Lyst 0.409280587 NA NA 8.39E−50 NA Myo1e 0.614341001 NA NA 9.34E−50 NA Tmem87b 0.434399269 NA NA 1.07E−49 NA Slc10a2 0.299006165 NA NA 2.04E−49 NA Gnl3 0.575970422 NA NA 2.63E−49 NA Lcn2 0.412194792 NA NA 2.72E−49 NA Jmjd1c 0.636619821 NA NA 3.43E−49 NA Cox7a2 −0.650338386  −0.363458039  NA 2.00E−48 5.69E−35 Cltc 0.784985399 0.438067775 NA 3.05E−48 2.75E−44 Rarres2 −0.552194576  −0.266616471  NA 3.29E−48 1.17E−31 Sc5d −0.500900917  0.345016882 NA 2.09E−27 3.57E−48 Ndufa6 −0.613649978  −0.306815302  NA 4.43E−48 4.71E−27 2-Mar 0.55994977  NA NA 4.66E−48 NA Hspa13 NA 0.354844877 NA NA 7.52E−48 Btg1 0.458007046 NA NA 1.02E−47 NA Pah −0.52207695  NA NA 1.25E−47 NA Leap2 −0.671300937  −0.274778129  NA 1.25E−47 1.45E−22 Cytip 0.267599208 NA NA 1.05E−46 NA Clpx NA −0.404735614  NA NA 1.07E−46 Sdc3 0.359804895 NA NA 1.11E−46 NA mt-Tm NA 0.284684642 NA NA 1.20E−46 Gm24187 0.431940663 NA NA 1.37E−46 NA Stk40 0.536418312 NA NA 2.15E−46 NA Cyp2c50 −0.661823297  −0.290483498  NA 2.92E−46 1.48E−24 Cfp 0.356178244 NA NA 6.11E−46 NA Dot1l 0.397036294 NA NA 7.81E−46 NA Saa4 −0.571021905  0.375528565 NA 2.31E−40 1.16E−45 Atp8b1 NA 0.362807422 NA NA 1.42E−45 Mdn1 0.317989246 NA NA 1.53E−45 NA Ndufb2 −0.577154458  −0.341226284  0.251595204 5.29E−40 2.52E−28 Hsd17b2 −0.595878526  NA −0.313480586  3.18E−45 NA H2-Eb1 0.327872672 NA NA 3.30E−45 NA Cxadr 0.698450944 NA NA 4.99E−45 NA Gstm3 −0.411092337  −0.318590137  −0.598573335  1.22E−06 2.69E−10 Cpb2 −0.321495225  0.322179327 NA 4.76E−14 5.47E−45 Spcs3 NA 0.394206972 NA NA 9.16E−45 Cd302 −0.549925078  NA NA 1.10E−44 NA Plg NA 0.261736006 NA NA 1.34E−44 Lactb2 −0.596505052  NA NA 1.72E−44 NA Tsr1 0.360287403 NA NA 2.32E−44 NA Igfbp2 −0.298981027  −0.345087789  NA 1.25E−14 4.02E−44 Rps2 −0.387862655  −0.384454173  −0.374246561  2.13E−20 6.76E−40 Dgkd 0.370844881 NA NA 1.62E−43 NA Cml1 −0.61424052  −0.326909468  NA 1.70E−43 2.10E−29 Sorl1 0.306655621 NA NA 1.87E−43 NA Tra2a 0.712328169 NA NA 2.35E−43 NA Dcxr −0.440851615  −0.410666503  NA 2.61E−26 2.61E−43 Aadac −0.619958028  −0.40376663  NA 4.18E−43 5.65E−43 Ppib −0.589699514  NA −0.260118322  1.14E−42 NA Lect2 −0.626967771  NA NA 1.41E−42 NA Tlcd2 −0.594498821  NA NA 1.60E−42 NA Lpin1 NA NA 0.277494868 NA NA Ttc39c −0.636274928  NA −0.374504475  2.03E−42 NA Tacc2 0.329332932 NA NA 3.95E−42 NA Gchfr −0.554783473  −0.386867237  NA 5.12E−39 4.46E−42 Tmed7 NA 0.386771014 NA NA 6.68E−42 Usp9x 0.318385696 0.407617259 NA 2.35E−09 9.98E−42 Aldh1a1 −0.478797447  NA NA 1.02E−41 NA Sdad1 0.312421192 NA NA 1.30E−41 NA Fdx1 −0.623439092  −0.344715083  NA 1.55E−41 4.65E−26 Eef2 0.525855561 0.270115373 NA 2.71E−41 2.54E−28 Gstz1 −0.464086834  NA NA 2.81E−41 NA Ptpn1 0.41633121  NA NA 3.51E−41 NA Tnfrsf1a 0.599573483 NA NA 3.86E−41 NA Rad54l2 0.388705156 NA NA 4.52E−41 NA Il13ra1 0.278527191 0.30296595  NA 6.54E−12 4.97E−41 Pemt −0.551184095  NA NA 7.86E−41 NA Acss2 −0.620071374  NA −0.258362678  8.55E−41 NA 1-Mar −0.477762617  NA NA 9.43E−41 NA Ddx3x 0.656890035 NA NA 1.07E−40 NA Hs3st3b1 NA 0.343007923 NA NA 1.60E−40 Acox1 NA 0.275171428 NA NA 1.78E−40 Atp5j2 −0.51308051  NA NA 3.32E−40 NA 8430408G22Rik −0.50210224  NA NA 4.85E−40 NA Ndufb9 −0.503828812  NA NA 5.48E−40 NA Hif1a 0.516911277 NA NA 5.71E−40 NA Hes6 −0.561302344  NA −0.262263942  5.81E−40 NA Tsku 0.36762763  NA NA 6.05E−40 NA Dnajc12 NA 0.322094554 NA NA 1.14E−39 Eaf1 0.521796522 NA NA 1.19E−39 NA Qdpr −0.52357376  NA NA 1.45E−39 NA Atp5f1 −0.517061165  −0.28724025  NA 2.05E−39 1.01E−28 Gm4076 NA −0.325469418  −0.308321155  NA 1.37E−35 Uso1 NA 0.388069473 NA NA 3.58E−39 Maff 0.355300257 NA NA 4.89E−39 NA Qsox1 NA 0.342352868 NA NA 9.20E−39 Adh4 −0.526868306  0.376928101 NA 1.92E−38 1.20E−30 Chic2 0.419790279 NA NA 2.33E−38 NA Eef1b2 NA NA −0.317323205  NA NA Adh5 −0.491433382  NA NA 2.88E−38 NA Itih2 0.501091194 0.298659728 NA 3.43E−38 6.17E−35 Gjb2 0.60822545  0.391136188 NA 1.12E−27 3.74E−38 Fabp2 −0.615569339  −0.39219613  NA 4.18E−38 3.19E−36 Slc20a1 0.357248475 NA NA 6.66E−38 NA Slc3a1 NA 0.340997565 NA NA 7.10E−38 Mup2 −0.50447051  −0.274243623  −0.55305847  9.59E−13 1 Abca1 0.724477701 0.439378423 NA 8.81E−38 4.14E−37 Ndufa7 −0.555912274  NA NA 1.32E−37 NA Lgmn 0.484586871 NA NA 1.80E−37 NA Gamt −0.560282685  NA NA 2.41E−37 NA Bcl3 0.289017645 NA NA 3.63E−37 NA Hint2 −0.424321102  −0.37016853  NA 5.24E−24 6.90E−37 Mpc2 −0.482839417  NA NA 7.20E−37 NA Atxn1 NA 0.304881734 NA NA 9.14E−37 Cyp2c54 −0.39493764  −0.326859698  0.250387024 1.78E−20 3.25E−32 Fos NA 0.432003299 NA NA 1.43E−36 St3gal1 0.528739882 NA NA 1.81E−36 NA Msn 0.260172491 NA NA 1.86E−36 NA Sds 0.390741627 −0.407006722  0.297273523 7.29E−12 2.82E−36 Rpn1 NA 0.41242919  NA NA 5.16E−36 Ucp2 0.261164666 NA NA 8.74E−36 NA Tcerg1 0.357549618 NA NA 1.14E−35 NA Akr1c20 −0.554152364  NA NA 1.48E−35 NA Dst 0.510971252 0.324301394 NA 2.08E−26 1.75E−35 Dstn NA 0.324301394 NA NA 1.75E−35 S100a1 −0.374338118  −0.376186192  NA 1.68E−18 1.76E−35 Sar1b −0.307930709  −0.317607513  NA 2.07E−14 1.79E−35 Crp −0.506869364  NA NA 2.22E−35 NA Pfkfb2 0.290016291 NA NA 2.41E−35 NA Gm4952 −0.49867829  NA NA 4.03E−35 NA Ndufb6 −0.507682563  −0.306403298  NA 4.30E−35 4.45E−28 Vsig4 0.483290635 NA NA 4.48E−35 NA Hao1 NA 0.32303248  NA NA 4.98E−35 Tubb2a 0.749433744 NA NA 5.17E−35 NA Arl4d −0.507228317  NA NA 6.71E−35 NA mmu-mir-6236 0.520569164 0.787474192 −0.429737333  2.18E−05 7.24E−35 Apobec1 0.305082858 NA NA 9.49E−35 NA Akr1c14 −0.518570798  NA NA 1.08E−34 NA Tmem30a NA 0.332760453 NA NA 1.95E−34 Cfhr2 −0.44846316  −0.321928662  −0.306325678  4.83E−25 4.87E−29 Slc41a2 0.260152635 0.278262888 NA 6.42E−16 2.13E−34 Ipo7 0.324580152 0.25915239  NA 1.14E−13 2.19E−34 Tsc22d2 0.391059638 NA NA 2.43E−34 NA Cyb5r3 NA 0.339033056 NA NA 3.10E−34 Apol7a −0.492294435  NA NA 3.11E−34 NA Fxyd1 −0.479908398  −0.311759144  NA 2.89E−33 3.83E−34 Cox5b −0.498783616  −0.337825031  NA 4.68E−34 1.67E−32 Rplp1 −0.504662964  −0.286640389  NA 4.91E−34 5.94E−23 Ugdh 0.633076584 NA NA 5.17E−34 NA H2-Aa 0.327934784 NA NA 6.84E−34 NA H3f3b 0.702914634 NA NA 7.03E−34 NA Ppan 0.272410087 NA NA 7.48E−34 NA Ugt2a3 −0.307528085  −0.333441405  NA 3.75E−16 8.21E−34 Xbp1 0.603165814 NA NA 9.59E−34 NA Tjp2 0.411461753 NA NA 1.10E−33 NA Tatdn2 0.373296072 NA NA 1.22E−33 NA Hibadh −0.499409672  NA NA 1.26E−33 NA Pten NA 0.355902258 NA NA 1.92E−33 Ctsl 0.530101805 NA NA 1.93E−33 NA Hspb8 0.633933124 NA NA 2.00E−33 NA Atp5j −0.48373528  NA NA 3.59E−33 NA Usp4 0.279964381 0.324732042 NA 8.83E−09 4.02E−33 Nolc1 0.47222269  NA NA 4.11E−33 NA Ier5 0.288994609 NA NA 4.64E−33 NA Lonp2 −0.467365882  NA NA 5.23E−33 NA Rpl32 −0.532218378  −0.254910119  −0.284689184  1.10E−32 2.90E−16 Rrbp1 NA 0.306944991 NA NA 1.11E−32 Dio1 −0.545283744  NA NA 1.11E−32 NA Tmem256 −0.518510202  NA NA 1.19E−32 NA Pdia6 −0.389966782  0.336506977 NA 5.65E−20 1.21E−32 Ssr1 NA 0.327818552 NA NA 1.30E−32 Gm5096 NA −0.363089147  NA NA 1.95E−32 Mcm10 −0.487427572  NA NA 2.29E−32 NA Ibtk NA 0.331106132 NA NA 4.10E−32 Nit2 −0.485940613  NA NA 4.49E−32 NA Ppm1k −0.558394496  NA NA 6.56E−32 NA Son 0.542911509 NA NA 7.13E−32 NA Adh6-ps1 −0.418504072  NA NA 9.38E−32 NA Selenbp1 −0.493707332  −0.280021704  NA 9.52E−32 1.67E−21 Uggt1 NA 0.284457726 NA NA 1.12E−31 Efna1 NA 0.336097237 NA NA 1.73E−31 Ssr4 −0.507577243  NA NA 1.87E−31 NA Ndufs6 −0.537929827  −0.359160953  NA 2.00E−31 4.72E−31 1600014C10Rik −0.498182953  NA NA 2.43E−31 NA Gas5 NA −0.336153154  NA NA 2.74E−31 Nop56 0.265670844 NA NA 2.87E−31 NA Etfb −0.365490277  NA NA 4.01E−31 NA Dusp16 0.46051738  NA NA 4.23E−31 NA Rora 0.644354953 NA NA 5.02E−31 NA Nedd4 0.281232817 0.377388355 NA 4.90E−18 6.69E−31 Epb4.1 0.562789274 NA NA 1.67E−30 NA Csde1 0.315554781 0.326883793 NA 2.59E−06 1.68E−30 Ranbp2 0.598499679 0.26594209  NA 2.18E−30 6.71E−19 Kmo −0.384440188  0.302208311 NA 6.51E−22 3.26E−30 Ndufa13 −0.43876131  NA NA 3.68E−30 NA Rnd3 0.36548808  NA NA 3.93E−30 NA Prkd3 NA 0.366517526 NA NA 3.93E−30 Nr5a2 NA 0.322039014 NA NA 5.05E−30 Gm23388 0.416208382 NA NA 5.50E−30 NA Ddx5 0.522944475 NA NA 5.90E−30 NA Blvrb −0.545112721  NA NA 6.23E−30 NA Lrp1 NA 0.505128824 NA NA 6.85E−30 Cfi NA 0.251606433 NA NA 7.20E−30 Mmp14 0.288913135 NA NA 7.66E−30 NA Plec 0.467512335 NA NA 8.30E−30 NA Rab1 NA 0.352627435 NA NA 1.03E−29 Jak1 0.603850485 0.254122657 NA 1.34E−29 1.20E−17 Slco1a1 −0.362843757  NA −0.295640242  2.16E−16 NA Errfi1 0.393680047 NA NA 1.52E−29 NA Slc38a4 NA 0.263698621 NA NA 2.48E−29 Uqcr10 −0.45190185  NA NA 2.60E−29 NA Nab1 NA 0.33421071  NA NA 3.00E−29 Il6st 0.316786986 0.333486533 NA 1.69E−06 3.02E−29 Mpc1 −0.280163495  −0.281762702  NA 1.13E−10 3.39E−29 Cmah NA 0.361552447 NA NA 5.19E−29 Calu NA 0.304112196 NA NA 5.69E−29 Mlec NA 0.324558531 NA NA 7.94E−29 Tm4sf4 0.512552747 NA NA 1.16E−28 NA Hal NA NA 0.280113531 NA NA Cmbl −0.442706435  −0.312422041  NA 2.71E−26 1.48E−28 Baz1a 0.259610685 NA NA 1.78E−28 NA Ak3 NA 0.289040998 NA NA 1.86E−28 Nrp1 0.360791537 0.334097753 NA 2.25E−08 1.93E−28 Gpt2 0.539114072 NA NA 2.49E−28 NA Etf1 0.559444816 NA NA 2.60E−28 NA Hook1 NA 0.327423989 NA NA 3.21E−28 Ndufb4 −0.453693039  −0.325145539  NA 2.93E−26 3.64E−28 Lgr4 NA 0.268964381 NA NA 9.73E−28 Lrrc59 0.377173076 0.318083941 NA 1.88E−10 1.35E−27 Dkc1 0.32575964  NA NA 1.54E−27 NA Stard10 −0.338316568  NA NA 1.68E−27 NA Hpx −0.303288229  NA NA 1.79E−27 NA Etnk1 0.315992963 0.352068809 NA 1.00E−05 1.82E−27 Agmat −0.471832829  NA NA 2.33E−27 NA Stard4 NA 0.351527506 NA NA 2.40E−27 Cyp39a1 0.351128984 NA NA 2.44E−27 NA Malat1 0.920628097 NA NA 2.62E−27 NA Dusp6 0.59164596  NA NA 2.71E−27 NA Ywhag 0.58241474  NA NA 3.05E−27 NA Adipor2 −0.473791512  NA NA 3.14E−27 NA Arcn1 NA 0.327775216 NA NA 3.29E−27 Serp1 NA 0.312399212 −0.267566027  NA 3.50E−27 Ifitm3 −0.425091425  NA −0.254348675  1.16E−25 NA Ces3b −0.36637965  −0.286685415  −0.263292817  6.63E−22 1.58E−25 Fcna 0.377428055 NA NA 5.71E−27 NA App 0.361832458 NA NA 6.12E−27 NA Cyp2c67 −0.463488581  NA NA 1.02E−26 NA Lrrfip1 0.445928709 NA NA 1.19E−26 NA Dhrs3 −0.467621234  NA NA 1.25E−26 NA Rpl36a1 −0.475541391  NA NA 1.26E−26 NA Cml2 −0.397916138  0.265441744 NA 4.33E−26 1.85E−26 Ppp1r3b −0.402657788  NA NA 2.29E−26 NA Eif4g1 0.374860037 0.310782755 NA 3.98E−13 2.42E−26 Ptpn12 0.33417878  NA NA 5.69E−26 NA Pik3c2a 0.324870962 0.25938652  NA 1.17E−09 5.98E−26 Cyp4a12a −0.456827492  NA 0.277051162 6.69E−26 NA Mug2 0.368295871 0.370406564 NA 9.47E−13 6.96E−26 Lman1 NA 0.29860668  NA NA 9.00E−26 Hspe1 −0.480734946  −0.290582957  0.281318916 9.37E−26 1.53E−19 Mrpl14 −0.459040925  NA NA 9.74E−26 NA Zfp683 −0.421689112  −0.421395009  NA 5.25E−09 1.05E−25 Mak16 0.317126116 NA NA 1.09E−25 NA Acsl4 0.298529302 0.314743242 NA 0.000351815 1.14E−25 Copa NA 0.345094339 NA NA 1.16E−25 mt-Atp6 −0.47818742  −0.573743033  0.323426357 1.61E−07 1.31E−25 Uqcrh −0.429164519  NA NA 1.41E−25 NA Slc38a3 −0.40978981  NA NA 1.45E−25 NA Minos1 −0.455548025  NA NA 2.00E−25 NA Ebpl −0.450334658  NA NA 2.09E−25 NA Atox1 −0.446203219  NA NA 2.48E−25 NA Tbc1d15 0.488646353 NA NA 2.52E−25 NA Aox3 −0.333319828  0.287845433 NA 2.16E−15 2.60E−25 Map2k3 0.434654367 NA NA 2.73E−25 NA Vkorc1 −0.404176916  −0.297366597  NA 3.54E−22 3.15E−25 Cyp7a1 −0.431201844  NA NA 3.19E−25 NA Trip12 NA 0.328304235 NA NA 3.31E−25 Hpgd −0.387752401  NA NA 3.49E−25 NA Lmo4 0.320534245 NA NA 3.97E−25 NA Cyb5b −0.423345561  NA NA 4.82E−25 NA Klf15 −0.451831953  NA NA 5.02E−25 NA Gnl2 0.390473036 NA NA 5.63E−25 NA 3110043O21Rik 0.269386631 NA NA 5.64E−25 NA Asgr1 −0.385655364  NA NA 6.52E−25 NA Mtus1 NA 0.362060296 NA NA 7.17E−25 Cyp2j5 −0.398305774  NA NA 7.33E−25 NA Mup1 −0.737727332  −0.261837735  −0.556836871  2.63E−21 1 Prdx5 −0.28208825  −0.260937182  NA 2.68E−15 8.22E−25 Chd1 0.378763061 NA NA 8.51E−25 NA Rarres1 −0.455632451  NA −0.291851226  8.53E−25 NA Sel1l NA 0.33595882  NA NA 8.76E−25 Arl5a NA 0.264805346 NA NA 1.52E−24 Mpeg1 0.493478112 NA NA 1.80E−24 NA Wdr43 0.343830267 NA NA 1.89E−24 NA Aff4 0.616309327 NA NA 1.96E−24 NA Timm13 −0.432961802  NA NA 2.46E−24 NA 1500017E21Rik −0.460997215  NA NA 2.47E−24 NA Nop10 −0.291908137  −0.264928395  NA 3.59E−14 2.62E−24 Serpina12 −0.453399356  NA −0.324744036  1.67E−21 NA Fam107b 0.463320341 NA NA 2.90E−24 NA Cep85l 0.277893187 NA NA 3.24E−24 NA Srpr NA 0.305179041 NA NA 4.78E−24 Narf NA 0.262933124 NA NA 6.15E−24 2410015M20Rik −0.402123463  NA NA 6.84E−24 NA Gtpbp4 0.482239467 NA NA 6.84E−24 NA Prdx4 −0.417588892  −0.307442113  −0.251975081  1.27E−20 6.96E−24 Ccs −0.426694207  NA NA 7.67E−24 NA Rps15 −0.455155041  −0.356137747  NA 4.49E−19 7.79E−24 Tns1 0.434939232 NA NA 8.90E−24 NA Esd −0.280760023  −0.25379488  NA 1.14E−13 9.90E−24 Ncl 0.48450982  NA NA 1.05E−23 NA Stom 0.323229029 NA NA 1.13E−23 NA Amacr −0.413582585  NA NA 1.14E−23 NA Sco2 −0.260508515  −0.292870629  NA 5.95E−07 1.32E−23 Glo1 −0.406574019  NA NA 1.87E−23 NA Mcl1 0.570934356 NA NA 2.05E−23 NA Mybbp1a 0.431161557 NA NA 2.11E−23 NA Nars 0.437769953 0.353230364 NA 7.84E−17 2.87E−23 Slc38a10 NA 0.285548034 NA NA 2.98E−23 Gm10800 0.562597493 NA NA 3.19E−23 NA Stt3b NA 0.319405267 NA NA 3.84E−23 Srp72 NA 0.310685136 NA NA 5.31E−23 Prrc2c 0.439271845 NA NA 6.04E−23 NA Zyx 0.298338034 NA NA 6.24E−23 NA Sc4mol −0.326170476  −0.273479653  NA 7.58E−15 6.26E−23 Mrp63 −0.442201567  NA NA 7.79E−23 NA Arg1 0.317948822 NA NA 8.62E−23 NA Arhgef12 0.590764816 0.304679431 NA 8.83E−23 1.41E−20 Acsm1 −0.369245009  NA NA 9.63E−23 NA Mat2a 0.482570924 NA NA 1.45E−22 NA Cars 0.315814572 NA NA 1.93E−22 NA Rps9 −0.371793799  −0.313951151  NA 1.65E−17 1.94E−22 Ell2 0.417241283 0.288090516 NA 8.49E−12 2.55E−22 Gm24245 0.546463773 0.42420314  NA 4.23E−18 3.25E−22 Rpl13a −0.381462137  NA NA 3.58E−22 NA Bzw1 0.294810535 0.284147153 NA 1.35E−07 3.59E−22 Grlf1 NA 0.295046691 NA NA 3.99E−22 Bbox1 −0.408245616  NA NA 4.17E−22 NA Map3k5 0.33471162  NA NA 4.76E−22 NA Pecr −0.398084036  NA NA 4.93E−22 NA Ndufa3 −0.41160475  NA NA 5.38E−22 NA Tmem14c −0.368514287  NA NA 6.04E−22 NA Atp13a3 0.394480252 0.303730845 NA 2.58E−11 6.61E−22 Pxk 0.281854648 NA NA 6.95E−22 NA Rps18 −0.488540797  NA NA 8.18E−22 NA Mrps24 −0.390380395  NA NA 8.75E−22 NA Mtss1 NA 0.287581972 NA NA 1.08E−21 Gjb1 −0.31656535  NA NA 1.13E−21 NA Edem1 NA 0.286881059 NA NA 1.13E−21 Spp2 −0.382096801  NA NA 1.28E−21 NA Kif5b 0.50116686  NA NA 1.57E−21 NA Acly NA 0.328803101 NA NA 1.74E−21 Rpl13 −0.298816085  −0.299693639  NA 1.55E−10 1.78E−21 1110001J03Rik −0.432785224  NA NA 2.04E−21 NA Dync1li1 0.262406206 NA NA 2.23E−21 NA Ndufa2 −0.396473631  NA NA 2.46E−21 NA Txndc5 NA 0.290124872 NA NA 3.56E−21 Psme1 −0.394006165  NA NA 3.58E−21 NA Ppp1r12a 0.356295305 NA NA 3.60E−21 NA Bphl −0.40747923  NA NA 5.02E−21 NA Trf −0.261883505  NA NA 5.32E−21 NA Cyp2c68 −0.398830868  NA NA 7.05E−21 NA Trib1 0.331693479 0.287458438 NA 0.001450331 7.49E−21 Akr1c19 NA −0.272667086  NA NA 7.78E−21 Cpne3 NA 0.258007443 NA NA 8.12E−21 Pnpla7 NA 0.29608325  −0.301626901  NA 1.01E−20 Dnajb11 NA 0.315357308 NA NA 1.04E−20 Phc2 0.31203626  NA NA 1.14E−20 NA Atp6v1f NA −0.252893521  NA NA 1.18E−20 Tars 0.492059498 NA NA 1.28E−20 NA Ctnnb1 NA 0.295681078 NA NA 1.58E−20 Id3 NA −0.351088732  NA NA 1.84E−20 Tmem243 −0.379053275  −0.26555147  NA 2.52E−19 2.35E−20 Eci1 NA −0.276383144  NA NA 2.48E−20 Lap3 −0.364371999  NA NA 2.65E−20 NA Cebpa −0.39155301  NA NA 3.89E−20 NA Tfpi2 −0.366342462  NA NA 4.58E−20 NA Il6ra 0.304392668 NA NA 5.08E−20 NA Cald1 0.373703655 0.258910981 NA 3.11E−13 5.69E−20 Neat1 0.63740381  NA NA 5.72E−20 NA Ptprf NA 0.307126385 NA NA 6.50E−20 Uqcrb −0.408416744  NA NA 6.59E−20 NA Ostc NA 0.265829876 NA NA 7.22E−20 Sec31a NA 0.263042758 NA NA 7.68E−20 Mbnl1 0.451258107 0.25020478  NA 9.50E−20 2.20E−15 Osbpl9 NA 0.278773264 NA NA 1.04E−19 Alad −0.420641438  NA NA 1.16E−19 NA Gch1 −0.269053605  −0.282499843  NA 1.54E−09 1.62E−19 Lrrfip2 0.373099277 NA NA 1.85E−19 NA Ireb2 NA 0.265741209 NA NA 1.87E−19 Cisd1 −0.372694857  NA NA 2.37E−19 NA Mocs2 −0.346681141  NA NA 2.62E−19 NA Coa6 −0.411409685  NA NA 2.73E−19 NA Mrc1 0.340444916 NA NA 2.90E−19 NA Copb2 NA 0.283928956 NA NA 3.01E−19 Stk17b 0.291050054 NA NA 3.56E−19 NA Ghr −0.364775879  NA NA 3.66E−19 NA Ptp4a1 0.262691158 NA NA 3.82E−19 NA Osbpl1a NA 0.272788799 NA NA 4.18E−19 Atp5g3 −0.300221819  NA NA 4.43E−19 NA Cyp27a1 −0.373510332  −0.251578373  NA 3.99E−18 4.44E−19 Akr1a1 −0.326935362  NA NA 4.63E−19 NA Atp5c1 −0.347648538  NA NA 5.04E−19 NA Nme1 −0.432885306  NA −0.285705103  5.43E−19 NA Azin1 NA 0.270139699 NA NA 6.16E−19 Purb 0.35248294  NA NA 6.99E−19 NA Timm8b −0.393581904  NA NA 8.39E−19 NA Uhrf1bp1l 0.419802385 NA NA 8.66E−19 NA Sfpq 0.393977901 NA NA 9.08E−19 NA Gsk3b 0.406458835 NA NA 9.12E−19 NA Iqgap2 NA 0.254698841 NA NA 9.72E−19 Cideb −0.368365389  −0.27071201  NA 5.77E−18 1.02E−18 Ndufc2 −0.425284817  −0.308039389  NA 1.31E−18 1.02E−18 Palld 0.341357023 NA NA 1.34E−18 NA D10Jhu81e −0.395730917  NA NA 1.93E−18 NA Pxmp2 −0.367129885  NA NA 2.40E−18 NA 15-Sep −0.409167133  NA NA 2.53E−18 NA Smg1 0.334990596 NA NA 2.85E−18 NA Aass 0.477517138 NA NA 3.07E−18 NA Hnrnpdl 0.397994117 NA NA 3.09E−18 NA Akap11 0.346362286 NA NA 4.54E−18 NA Nedd4l 0.281232817 NA NA 4.90E−18 NA Jhdm1d 0.304101624 NA NA 4.92E−18 NA 1500011K16Rik −0.329639846  NA NA 5.16E−18 NA Rps3 −0.349320751  NA NA 5.25E−18 NA Slc22a30 −0.374598404  NA −0.295400819  5.26E−18 NA Erp44 NA 0.279450299 NA NA 5.51E−18 Coro1c 0.306679199 NA NA 6.74E−18 NA Ptpn2 0.273418437 NA NA 7.37E−18 NA Commd6 −0.364529559  NA NA 7.88E−18 NA Fitm1 −0.324153911  NA NA 7.90E−18 NA Dgat2 −0.343266251  NA NA 8.35E−18 NA Surf4 NA 0.258577589 NA NA 9.74E−18 Gm10801 0.265934225 NA NA 1.30E−17 NA Cox6b1 −0.362017449  NA NA 1.47E−17 NA Adtrp −0.366413277  NA NA 1.53E−17 NA Ankrd11 0.415626852 NA NA 1.70E−17 NA Ccbl1 −0.36488302  NA NA 2.18E−17 NA Ftl1 −0.26029441  −0.349777423  −0.29880847  0.34648571  2.43E−17 Prkaa2 NA 0.263640766 NA NA 2.46E−17 Arl6ip1 −0.364945533  NA NA 2.55E−17 NA Egr1 0.584558888 NA NA 2.80E−17 NA Dnajb9 NA 0.25864192  NA NA 2.89E−17 Smdt1 −0.367317155  NA NA 3.21E−17 NA Ddc −0.360752783  NA NA 3.48E−17 NA Ndufc1 −0.344432714  NA NA 3.78E−17 NA Ndufb8 −0.348076577  NA NA 3.81E−17 NA Zbtb20 0.471532978 0.379090332 NA 1.83E−11 4.06E−17 Xiap NA 0.26016306  NA NA 4.75E−17 Tjp1 0.286163863 NA NA 4.89E−17 NA Anp32a −0.316957742  NA NA 5.23E−17 NA Ide NA 0.251691529 NA NA 5.60E−17 Ehhadh NA −0.250472633  NA NA 7.29E−17 Sptbn1 0.42268289  NA NA 7.32E−17 NA Mbl2 −0.346518253  NA NA 7.59E−17 NA Kpnb1 NA 0.280415627 NA NA 7.91E−17 Mien1 −0.370437762  NA NA 8.08E−17 NA Gne −0.425142761  NA NA 9.04E−17 NA Bola3 −0.368862428  NA NA 1.08E−16 NA Akap13 0.495253767 NA NA 1.14E−16 NA Hist1h1c −0.300906532  NA NA 1.17E−16 NA Nr2f6 −0.375433952  NA NA 1.37E−16 NA Ces1f −0.312589958  NA NA 1.45E−16 NA Ndufv3 −0.397145193  NA NA 1.45E−16 NA Cast 0.400886525 NA NA 1.50E−16 NA Golga4 0.352084678 0.271769698 NA 3.49E−05 1.56E−16 Apom −0.302410414  NA NA 1.68E−16 NA Ebp −0.355328266  NA NA 1.79E−16 NA Gpam NA 0.250377871 NA NA 1.86E−16 Edf1 −0.381679393  NA NA 1.87E−16 NA Srebf1 NA 0.27619787  NA NA 1.90E−16 Ndufs8 −0.361439192  NA NA 1.93E−16 NA Eprs 0.37008595  0.301270543 NA 1.04E−06 1.94E−16 Ndufa1 −0.364515751  NA NA 1.96E−16 NA Litaf 0.394366845 NA NA 2.04E−16 NA H6pd 0.343718187 0.261357904 NA 9.26E−07 2.22E−16 Bptf 0.324463857 NA NA 2.66E−16 NA Ifrd1 0.490389826 NA NA 2.92E−16 NA Plk3 0.416624571 NA NA 3.12E−16 NA Nadk2 NA 0.257852312 NA NA 3.23E−16 Myl12a 0.390780681 NA NA 3.32E−16 NA Psmb1 −0.358482353  NA NA 3.95E−16 NA Baat −0.308582001  NA NA 4.31E−16 NA Cnpy2 −0.372850093  NA NA 4.94E−16 NA Bhmt2 −0.311413339  NA NA 5.24E−16 NA Gstm4 −0.380861133  NA NA 5.61E−16 NA Chac2 −0.286511682  NA NA 6.00E−16 NA Mettl20 −0.331367185  NA NA 6.50E−16 NA Bckdha −0.349979609  NA NA 6.82E−16 NA BC089597 NA 0.262237515 NA NA 6.90E−16 Sirt3 −0.345997558  NA NA 7.30E−16 NA Mdm2 0.328296258 NA NA 8.15E−16 NA Acy3 −0.313748988  NA NA 8.20E−16 NA Hsp90ab1 0.322748941 NA NA 8.34E−16 NA Mrpl12 −0.308200176  NA NA 9.04E−16 NA Fam120a NA 0.280043634 NA NA 9.81E−16 Atp5o −0.331628292  NA NA 9.93E−16 NA Fkbp4 −0.353366286  NA NA 1.01E−15 NA Cldn3 −0.314469359  NA NA 1.08E−15 NA Ipo5 0.268735631 NA NA 1.12E−15 NA Fpgs −0.34940945  NA NA 1.15E−15 NA Sdsl 0.259290764 NA NA 1.41E−15 NA Tgm2 0.399330712 NA NA 1.43E−15 NA Phlda1 0.549174347 NA NA 1.46E−15 NA Macf1 0.404177263 0.261666188 NA 4.26E−11 1.47E−15 Mrps18c −0.366291099  NA NA 1.60E−15 NA Sbno1 0.367100512 0.250529348 NA 2.44E−13 1.62E−15 Nedd8 −0.356380686  NA NA 1.86E−15 NA Magt1 NA 0.263295188 NA NA 1.95E−15 Sdhb −0.289642823  NA NA 2.09E−15 NA Ethe1 −0.333417645  NA NA 2.45E−15 NA Mdh1 −0.307657821  NA NA 3.99E−15 NA Nrip1 0.272854584 NA NA 4.11E−15 NA Lcp1 0.484011001 NA NA 4.22E−15 NA Srsf11 0.401209055 NA NA 4.47E−15 NA Shb 0.315236194 NA NA 4.68E−15 NA Bsg −0.31515012  NA NA 5.31E−15 NA Hibch −0.327130099  NA NA 6.26E−15 NA Mki67ip 0.318372964 NA NA 6.27E−15 NA Otc −0.29903416  NA NA 6.99E−15 NA Smap2 0.348911433 NA NA 9.52E−15 NA Nr0b2 −0.293010319  NA NA 1.07E−14 NA Pank1 −0.352650118  NA NA 1.09E−14 NA Ak2 −0.345102135  NA NA 1.13E−14 NA Rlim 0.31023282  NA NA 1.42E−14 NA Erbb2ip 0.333163506 0.279650574 NA 2.35E−07 1.69E−14 Huwe1 0.387931325 NA NA 1.75E−14 NA Hmgcs1 −0.349112403  NA NA 1.98E−14 NA Rps21 −0.364450868  NA NA 2.02E−14 NA Grhpr −0.353058662  NA NA 2.13E−14 NA Tm7sf2 −0.316381125  NA NA 2.28E−14 NA Txn1 −0.309123787  NA NA 2.50E−14 NA Sh3bgrl NA 0.25128227  NA NA 2.71E−14 0610011F06Rik −0.303688511  NA NA 2.80E−14 NA Psmb6 −0.319377533  NA NA 2.87E−14 NA Gm2788 −0.283138796  NA NA 2.89E−14 NA AW112010 −0.298104828  NA NA 3.17E−14 NA Dhdh −0.334814135  NA NA 4.04E−14 NA Sf1 0.30230624  NA NA 4.12E−14 NA Tbl1xr1 0.307509115 NA NA 4.15E−14 NA Coq9 −0.347936449  NA NA 4.20E−14 NA Il4ra 0.25739098  NA NA 4.44E−14 NA Tceb2 −0.32073626  NA NA 4.50E−14 NA Rps10 −0.33690905  NA NA 4.59E−14 NA Psme4 NA 0.262584214 NA NA 4.62E−14 Gm4951 −0.322087312  NA NA 5.37E−14 NA Pak2 0.281467155 NA NA 5.57E−14 NA Metap2 0.368604828 NA NA 6.59E−14 NA 2010107E04Rik −0.318247806  NA NA 7.21E−14 NA Prox1 NA 0.266329524 NA NA 7.66E−14 Ddx6 0.444275069 NA NA 7.70E−14 NA Pacsin2 0.370825053 NA NA 7.89E−14 NA Hdac11 −0.33684651  NA NA 8.63E−14 NA Ubl5 −0.303313218  NA NA 1.12E−13 NA Mettl7a1 −0.322098553  NA NA 1.21E−13 NA Larp4b 0.34214672  NA NA 1.22E−13 NA Uqcc2 −0.326858302  NA NA 1.27E−13 NA 1810022K09Rik −0.300081452  NA NA 1.29E−13 NA Selk −0.338314398  NA −0.289300641  1.79E−12 NA Dhx9 0.350364065 NA NA 1.41E−13 NA Psmb3 −0.330302519  NA NA 1.47E−13 NA Rexo2 −0.3263129    NA NA 1.48E−13 NA Hipk3 0.339385214 NA NA 1.58E−13 NA Cyp4f14 −0.295933211  NA NA 1.60E−13 NA Wdr26 0.432510772 NA NA 1.94E−13 NA Sec61b −0.290284119  NA NA 2.20E−13 NA Paqr9 −0.332341635  NA NA 2.23E−13 NA Tsc22d1 −0.299728636  NA NA 2.38E−13 NA Glyctk 0.297701904 NA NA 2.68E−13 NA Mapk6 0.256831906 NA NA 3.22E−13 NA Atp1b1 0.370203015 NA NA 3.27E−13 NA Aqp9 −0.310863805  NA NA 3.38E−13 NA Suco 0.250962583 NA NA 3.39E−13 NA Dync1h1 0.379607116 NA NA 4.50E−13 NA Ctsb 0.521310448 NA NA 4.83E−13 NA Tpr 0.440921219 NA NA 5.22E−13 NA Supt6 0.291294768 NA NA 5.48E−13 NA Lsmd1 −0.313140806  NA NA 5.95E−13 NA Kif21a 0.404170578 NA NA 6.46E−13 NA Sgk1 0.284303028 NA NA 7.18E−13 NA Proz NA 0.263204472 NA NA 7.77E−13 Romo1 −0.335854841  NA NA 7.99E−13 NA Cfhr1 −0.325332852  NA NA 8.01E−13 NA Deptor NA 0.260618372 NA NA 8.58E−13 Atp2b1 0.332096305 NA NA 9.01E−13 NA Rnf13 NA 0.255296715 NA NA 9.16E−13 Dhrs4 −0.332074421  NA NA 9.59E−13 NA Lasp1 NA 0.253021439 NA NA 9.93E−13 Tmem147 0.283785217 NA NA 1.00E−12 NA Fus 0.339324351 NA NA 1.03E−12 NA Yap1 0.328109852 NA NA 1.07E−12 NA Acads −0.32421998  NA NA 1.10E−12 NA Fam25c −0.297673676  NA NA 1.12E−12 NA Ndufb3 −0.327185415  NA NA 1.16E−12 NA Agpat2 −0.298159013  NA NA 1.22E−12 NA Bst2 −0.315565973  NA NA 1.52E−12 NA Caprin1 NA 0.262825966 NA NA 1.56E−12 Syncrip 0.27476476  NA NA 1.65E−12 NA Rnaseh2c −0.325683719  NA NA 1.67E−12 NA Cldn2 −0.251076838  NA NA 1.86E−12 NA Klf3 0.267357487 NA NA 1.89E−12 NA Tnks2 0.317626402 NA NA 1.91E−12 NA Derl2 −0.331734152  NA NA 2.28E−12 NA Ndufv2 −0.327639406  NA NA 2.48E−12 NA Eif4b 0.36816236  0.255987641 NA 3.78E−07 2.53E−12 Cyp4f15 −0.299840345  NA NA 2.53E−12 NA Brd2 0.571515166 0.266388486 NA 1.73E−11 2.65E−12 Copz1 NA 0.257722711 NA NA 2.65E−12 Ddx27 0.252155421 NA NA 3.46E−12 NA Mcee −0.31991829  NA NA 3.52E−12 NA Dnajc19 −0.316006732  NA NA 3.54E−12 NA Aldh4a1 −0.29070878  NA NA 3.75E−12 NA Fdps −0.266347718  NA NA 4.58E−12 NA Reep3 0.409014614 NA NA 5.12E−12 NA Car5a −0.308769058  NA NA 5.42E−12 NA Tmem37 −0.282207793  NA NA 6.77E−12 NA Tspo −0.315729205  NA NA 6.95E−12 NA Tspan31 −0.295881364  NA NA 7.18E−12 NA Atp11c NA 0.260536506 NA NA 7.22E−12 Atf6 0.377819844 NA NA 7.66E−12 NA Rpl14 −0.277637754  NA NA 7.87E−12 NA Med13 0.294918978 NA NA 7.95E−12 NA Sdr9c7 −0.259988635  NA NA 8.11E−12 NA Rps8 NA NA −0.274601282  NA NA Kpna1 0.32304803  NA NA 8.67E−12 NA Btaf1 0.275463861 NA NA 8.92E−12 NA Ddah1 −0.312000429  NA NA 9.85E−12 NA Ndufs4 −0.313160933  NA NA 1.01E−11 NA Fam214a −0.265769677  NA NA 1.02E−11 NA Rbm25 0.421459678 NA NA 1.03E−11 NA Ndufb10 −0.300358086  NA NA 1.04E−11 NA Slirp −0.308519262  NA NA 1.04E−11 NA Scaf11 0.359845436 NA NA 1.30E−11 NA Anapc13 −0.364181956  NA NA 1.31E−11 NA Arpc1b 0.259676842 NA NA 1.36E−11 NA Pnkd −0.292772175  NA NA 1.41E−11 NA Abcd3 −0.271805105  NA NA 1.44E−11 NA Hmgcr 0.416711628 NA NA 1.61E−11 NA Mxd1 0.297767874 NA NA 1.65E−11 NA Bet1 −0.296563627  NA NA 1.73E−11 NA Cela1 −0.272296838  NA NA 1.78E−11 NA Tmem160 −0.339044834  NA NA 2.24E−11 NA Snx10 0.285642594 NA NA 2.35E−11 NA Ubb −0.275030382  −0.259339434  −0.264432797  6.19E−10 2.58E−11 Lgals9 −0.269998113  NA NA 2.87E−11 NA Aadat −0.318627951  NA NA 3.04E−11 NA Mrpl33 −0.265447876  NA NA 3.06E−11 NA Tmem258 −0.27689533  NA NA 3.18E−11 NA Cyp2d40 −0.321717407  NA NA 3.46E−11 NA Birc6 0.344367807 NA NA 3.56E−11 NA Naprt1 −0.338143058  NA NA 4.15E−11 NA Agxt −0.258383387  NA NA 4.28E−11 NA Kdelr2 0.397729248 NA NA 4.46E−11 NA Stbd1 −0.273216024  NA NA 5.39E−11 NA Phf20l1 0.308488005 NA NA 5.49E−11 NA Tmprss6 −0.280234101  NA NA 5.62E−11 NA Gstk1 −0.282802747  NA NA 5.77E−11 NA Gadd45gip1 −0.304090556  NA NA 6.25E−11 NA Ubr4 0.330144527 NA NA 7.63E−11 NA Sigmar1 −0.305468332  NA NA 7.64E−11 NA Ythdc1 0.264130576 NA NA 8.40E−11 NA Psma6 −0.30353658  NA NA 8.48E−11 NA Acaa1a −0.301848759  NA NA 9.21E−11 NA Cyp2c55 −0.290435372  NA NA 9.36E−11 NA Proc −0.270719362  NA NA 9.66E−11 NA Mrpl20 −0.309348635  NA NA 1.03E−10 NA Myeov2 −0.305189789  NA NA 1.05E−10 NA Dnajc5 0.326483514 NA NA 1.16E−10 NA Kdm5a 0.351390096 NA NA 1.27E−10 NA Commd3 −0.265556375  NA NA 1.46E−10 NA Mrpl42 −0.284507519  NA NA 1.47E−10 NA Bdhl −0.293611347  NA NA 1.50E−10 NA Mrpl15 −0.291228504  NA NA 1.56E−10 NA Abcb11 −0.261778471  NA NA 1.57E−10 NA Ddost NA 0.250356033 NA NA 1.89E−10 Anxa5 0.365372347 NA NA 2.08E−10 NA Gsr 0.412829579 NA NA 2.10E−10 NA Atf4 0.341134734 NA NA 2.33E−10 NA Iah1 −0.292985785  NA NA 2.41E−10 NA Pdzd8 0.286270568 NA NA 2.46E−10 NA Fbxo21 −0.263087536  NA NA 2.85E−10 NA Ftsj3 0.255227431 NA NA 2.86E−10 NA C6 NA NA −0.26698766  NA NA Acot13 −0.288638646  NA NA 3.05E−10 NA Acat3 −0.311510623  NA NA 3.16E−10 NA Magi3 0.269961841 NA NA 3.24E−10 NA Cybb 0.377799564 NA NA 3.48E−10 NA Tmem242 −0.272538433  NA NA 3.57E−10 NA Mrpl41 −0.267412137  NA NA 3.73E−10 NA Sema4g −0.250459516  NA NA 3.89E−10 NA Cap1 0.325055169 NA NA 4.46E−10 NA Csrp3 −0.293996249  NA NA 4.47E−10 NA Hpn −0.268601326  NA NA 4.81E−10 NA Slc25a51 0.263985158 NA NA 6.14E−10 NA Spcs1 −0.26287037  NA NA 6.30E−10 NA Apof −0.252173807  NA NA 6.73E−10 NA Cep85 0.28389234  NA NA 6.87E−10 NA Aes −0.264214993  NA NA 7.53E−10 NA Pet100 −0.28003555  NA NA 7.60E−10 NA Gcat −0.258728349  NA NA 7.71E−10 NA Rps24 −0.262473665  NA NA 8.21E−10 NA Dcaf11 v0.281659388  NA NA 9.55E−10 NA Pmpcb v0.263615722  NA NA 1.03E−09 NA Lipc −0.254841484  NA NA 1.09E−09 NA Ptpn11 0.277804552 NA NA 1.15E−09 NA Ccdc50 0.285830087 NA NA 1.18E−09 NA Ivns1abp 0.356610399 NA NA 1.20E−09 NA Nqo2 −0.267802053  NA NA 1.22E−09 NA Abcg2 −0.280923445  NA NA 1.38E−09 NA Dera −0.267441985  NA NA 1.43E−09 NA Fasn NA 0.291406736 NA NA 1.44E−09 Rabac1 −0.265987205  NA NA 1.45E−09 NA Gm20594 0.295686612 −0.360000649  −0.356558629  1.60E−05 2.58E−08 Clic4 0.299795775 NA NA 1.64E−09 NA Ugt3a2 −0.258613351  NA NA 1.89E−09 NA Mvd −0.270409867  NA NA 1.91E−09 NA Ptpmt1 −0.255981462  NA NA 2.02E−09 NA 0610007P14Rik −0.257015045  NA NA 2.31E−09 NA Swi5 −0.262086804  NA NA 2.33E−09 NA Tpi1 −0.26157943  NA NA 2.35E−09 NA Plcxd2 −0.275192522  NA NA 2.48E−09 NA Tmem150a −0.253507791  NA NA 2.61E−09 NA Rnf169 0.333974467 NA NA 2.63E−09 NA Deb1 −0.267029156  NA NA 2.74E−09 NA Hsbp1 −0.286726926  NA NA 2.99E−09 NA Slc26a1 −0.28165635  NA NA 3.01E−09 NA Rsl1d1 0.346056141 NA NA 3.82E−09 NA Map3k2 0.251791147 NA NA 3.83E−09 NA Abcf1 0.303190272 NA NA 4.09E−09 NA Psma1 −0.256671259  NA NA 4.64E−09 NA Fam195a −0.264890901  NA NA 4.66E−09 NA Mrpl11 −0.268482417  NA NA 4.92E−09 NA Selo −0.257421903  NA NA 5.24E−09 NA Plbd2 0.264873115 NA NA 5.33E−09 NA Rap1b 0.340766029 NA NA 6.89E−09 NA Ppip5k2 0.320939415 NA NA 7.41E−09 NA Pcm1 0.265397644 NA NA 8.07E−09 NA Acsm5 −0.261394035  NA NA 8.53E−09 NA Rangap1 0.296226768 NA NA 1.08E−08 NA Rraga 0.262613483 NA NA 1.10E−08 NA 1110058L19Rik −0.258088587  NA NA 1.12E−08 NA Dsp 0.265533344 NA NA 1.15E−08 NA Ccnl1 0.256623048 NA NA 1.44E−08 NA Chmp4b 0.300153098 NA NA 1.52E−08 NA Ubr5 0.305718363 NA NA 1.72E−08 NA Net1 0.34785505  NA NA 1.84E−08 NA H2-D1 0.286522764 NA NA 2.31E−08 NA Srd5a1 −0.277347272  NA NA 2.35E−08 NA Papss2 −0.254475327  NA NA 2.73E−08 NA Dnaja2 0.372342331 NA NA 2.79E−08 NA Srrm2 0.328159189 NA NA 3.12E−08 NA Herc1 0.256188826 NA NA 3.26E−08 NA Gtf2a2 0.279207862 NA NA 3.58E−08 NA Pkp4 0.323033636 NA NA 4.02E−08 NA Trip11 0.347886673 NA NA 4.15E−08 NA Slc16a2 −0.251969763  NA NA 4.57E−08 NA Ctsc 0.361021766 0.300373343 NA 4.80E−08 9.04E−06 Megf9 0.276890033 NA NA 6.26E−08 NA Mrpl28 −0.269896048  NA NA 6.87E−08 NA Rpl34 −0.297598539  NA NA 8.13E−08 NA Mrpl34 −0.283750306  NA NA 8.42E−08 NA Mgea5 0.32630901  NA NA 9.07E−08 NA C1d −0.255261652  NA NA 9.45E−08 NA Gcgr −0.257636913  NA NA 1.04E−07 NA Sptan1 0.312663889 NA NA 1.10E−07 NA Zfp259 0.255636639 NA NA 1.10E−07 NA Xrn2 0.298471923 NA NA 1.28E−07 NA Hipk1 0.291600227 NA NA 1.40E−07 NA Alcam 0.323788815 NA NA 1.46E−07 NA Gnas 0.258853087 NA NA 1.47E−07 NA Mapkapk2 0.31382654  NA NA 1.63E−07 NA Coasy −0.253428655  NA NA 1.78E−07 NA Gars 0.257638792 NA NA 2.09E−07 NA Diap1 0.325941798 NA NA 2.19E−07 NA Rab6a 0.32343226  NA NA 2.23E−07 NA Pvrl2 −0.261260991  NA NA 2.66E−07 NA 2810428115Rik −0.263117928  NA NA 2.80E−07 NA Nucks1 0.355785584 NA NA 2.82E−07 NA Hnrnpu 0.339415607 NA NA 3.35E−07 NA Chuk 0.372437977 NA NA 5.21E−07 NA Serbp1 0.322652522 NA NA 5.43E−07 NA Ctnnd1 0.251848095 NA NA 5.48E−07 NA Nploc4 0.291804954 NA NA 5.69E−07 NA Zfp106 0.336920255 NA NA 6.34E−07 NA Arhgdia 0.256326455 NA NA 7.14E−07 NA BC005537 0.354337911 NA NA 1.05E−06 NA Akr1e1 −0.258207619  NA NA 1.09E−06 NA Eific 0.301979757 NA NA 1.10E−06 NA Tmem86b −0.258236533  NA NA 1.18E−06 NA Mrps12 −0.250441318  NA NA 1.26E−06 NA Cdh1 0.269696738 NA NA 1.61E−06 NA Ddx3y 0.339517654 NA NA 1.83E−06 NA Ndufa5 −0.251988986  NA NA 1.96E−06 NA Ppm1g 0.252225215 NA NA 2.04E−06 NA Elovl5 0.335236661 NA NA 2.54E−06 NA Impad1 0.32267465  NA NA 3.04E−06 NA Tab2 0.348412001 NA NA 3.51E−06 NA Cyp3a13 0.284411943 NA NA 4.93E−06 NA Pgls −0.274714156  NA NA 5.62E−06 NA Actr3 0.275997927 NA NA 5.66E−06 NA St3gal4 0.275033534 NA NA 5.81E−06 NA 4932438A13Rik 0.287850722 NA NA 7.97E−06 NA Abce1 0.279955892 NA NA 8.43E−06 NA Pde3b −0.258970093  NA NA 8.55E−06 NA Smoc1 0.26157412  NA NA 8.57E−06 NA 4931406C07Rik −0.254363633  NA NA 9.62E−06 NA Rmnd5a 0.318903459 NA NA 1.09E−05 NA Ash11 0.265693821 NA NA 1.23E−05 NA Sf3b1 0.28884767  NA NA 1.32E−05 NA Spag9 0.318820155 NA NA 1.33E−05 NA Nek7 0.291098417 NA NA 1.63E−05 NA Eif4a1 0.251906299 NA NA 2.25E−05 NA Usp7 0.287320099 NA NA 2.90E−05 NA Tbca −0.27261031  NA NA 3.43E−05 NA Pi4k2a 0.353561144 NA NA 3.46E−05 NA Prpf19 0.25876049  NA NA 3.47E−05 NA Usp34 0.285942387 NA NA 5.16E−05 NA Slc16a10 −0.254826191  NA NA 9.62E−05 NA Eea1 0.261201113 NA NA 0.000132332 NA Sars 0.276853119 NA NA 0.00019395  NA Herc4 0.267474882 NA NA 0.000255647 NA Gadd45a 0.282867411 NA NA 0.000337547 NA Bc1af1 0.26848767  NA NA 0.000425718 NA Gm5424 0.269800095 NA NA 0.000520866 NA Slc35d1 0.309435259 NA NA 0.000579989 NA Cu11 0.259206487 NA NA 0.000597201 NA Cu13 0.278802183 NA NA 0.000803381 NA Slc30a1 0.250570123 NA NA 0.000818871 NA Eifia 0.314713983 NA NA 0.00096785  NA Tln1 0.321033046 NA NA 0.001767724 NA Zfand5 0.28815165  NA NA 0.00189648  NA Glul NA NA 0.379494728 NA NA Eif4ebp1 0.261682735 NA NA 0.003063164 NA Hectd1 0.30802968  NA NA 0.003395612 NA Gldc 0.280156601 NA NA 0.00370491  NA Rassf3 0.291236708 NA NA 0.004723315 NA Nudt4 0.25418892  NA NA 0.007016738 NA Rock1 0.2607635  NA NA 0.009308994 NA Rbm39 0.265732671 NA NA 0.012545192 NA Abcc2 0.289681267 NA NA 0.018266512 NA Naa50 0.265659058 NA NA 0.019114384 NA Pa2g4 0.289349263 NA NA 0.02381992  NA Riok3 0.291562038 NA NA 0.055677881 NA Myo1b 0.262427327 NA NA 0.075213075 NA Eifib 0.250328103 NA NA 0.08550598  NA Ldlr 0.282025946 NA NA 0.146582345 NA Psap 0.257800256 NA NA 0.360973931 NA Gda 0.266276129 NA NA 0.627476336 NA Gnai2 0.281667665 NA NA 1       NA ID A48p avg_logFC p_val_adj Mup17 0 −2.354358557 0 Mup6 0 −2.032084932 0 Mup9 0 −2.004163996 0 Mup19 0 −2.396345291 0 Mup11 0 −3.213953203 0 Mup18 0 −1.727178347 0 Selenbp2 0 −1.190221952 0 Mup7 0 −1.115587848 0 Mup16 0 −1.602085539 0 mt-Co1 0 −1.43342755 0 Mup21 0 −1.008171912 0 mt-Nd4 0 −1.957424825 0 mt-Nd2 0 −1.241926048 0 mt-Cytb 0 −1.571232911 0 mt-Nd5  7.18E−267 −1.383591054 0 Serpina1e 0 −0.662045945 0 mt-Nd1  5.29E−267 −1.419683574 0 Mup3  7.73E−237 −0.806219448 0 Apoe 0 −0.421271729 0 Ces1c 0 0.466837177 0 Hmgcs2 0 0.629289122 0 Angptl3 0 0.7089371 0 Ang 0 0.7089371 0 Chchd10 0 0.720691838 0 Chchd1 0 0.720691838 0 Mat1a 0 1.000433202 0 Cyp4a10 0 1.135370857 0 Cyp4a14 0 1.704093543 0 Hbb-bs NA 2.862044849 0 Hmox1 NA 1.347585217 0 Gm26924 NA 1.419027502 0 Fga NA 0.828543313 0 n-R5-8s1 NA 1.252818829 0 Fgg NA 0.680530925 0 Fgb NA 0.744973762 0 Grip2 NA 0.877868293 0 Apoa2 NA −0.545518454 0 Apoh  8.57E−300 0.411790107  8.57E−300 Ttpa  4.46E−295 0.601240096  4.46E−295 Lars2 NA 1.711400221  1.38E−293 Gm13775  1.37E−292 −1.07808822  1.37E−292 Cdo1  3.00E−292 0.517045053  3.00E−292 Gm15564 NA 1.820580657  6.31E−292 S100a9 NA 1.342849617  5.31E−281 Tnfrsf12a NA 1.117506296  5.70E−279 Gm24601 NA 0.984391691  2.17E−275 Apoc2  3.07E−267 0.782126085  3.07E−267 Retsat  9.77E−266 0.681307283  9.77E−266 Ttr  5.79E−264 −0.530625643  5.79E−264 Sephs2 NA 0.889992859  2.83E−263 S100a8 NA 1.127879209  1.92E−258 Nudt7  2.67E−255 −1.564266936  2.67E−255 mt-Rnr2  1.98E−232 −0.778341998  5.04E−251 Ppl NA 0.879840886  9.97E−249 Serpina1a NA −0.675201963  4.32E−247 Acaa1b NA −0.85084133  4.51E−247 Sepp1  3.03E−246 0.448586822  3.03E−246 Srxn1 NA 1.878352012  2.22E−243 Apoc1  7.90E−242 −0.871282735  7.90E−242 Mup5  1.94E−240 −1.370621307  1.94E−240 Fgl1 NA 0.864933885  1.60E−238 Gpx1 NA −0.768556331  6.77E−238 Mt2 NA 2.06273693  1.90E−237 Ankrd55 1.45E−68 −1.8735659  4.38E−235 Mup15  1.22E−233 −1.316464146  1.22E−233 Mfsd2a  5.34E−233 0.666142747  5.34E−233 Mt1 1.20E−56 2.387707773  3.51E−232 Ndrg2  2.62E−223 0.41219937  2.62E−223 Ahsg  1.68E−221 0.292489576  1.68E−221 Hrg  3.81E−221 0.518895355  3.81E−221 mt-Co2  1.79E−173 −1.396543228  7.79E−219 Sult1a1  9.07E−216 0.560453494  9.07E−216 Agt  1.09E−213 0.520454244  1.09E−213 Cyb5 NA −0.71018958  8.36E−212 Fth1  5.81E−204 0.378367166  5.81E−204 Snord118  2.66E−203 0.617425052  2.66E−203 Fabp1 NA −1.016174848  1.10E−198 Slco1a4  1.65E−197 0.552641329  1.65E−197 mt-Rnr1  1.71E−195 −0.485399855  1.71E−195 Saa1  3.34E−194 −1.078220383  3.34E−194 Hilpda NA 0.778625914  3.64E−193 Gclc NA 1.902837282  1.67E−192 Cp  6.52E−192 0.436243259  6.52E−192 Igfbp4  1.54E−189 0.43528879  1.54E−189 Akr1c6  8.38E−143 −1.586259995  2.54E−187 Rbp4  1.88E−186 0.301440617  1.88E−186 Mup12  1.14E−185 −1.269973728  1.14E−185 Serpina1d NA −0.494007182  1.74E−184 Hspa5 2.27E−84 0.610549064  9.07E−184 Mgst1 NA −1.060154854  2.13E−181 Rdh7  6.63E−181 −0.418625957  6.63E−181 Apoc3  8.39E−179 −0.768781074  8.39E−179 Herpud1  9.68E−179 0.513571228  9.68E−179 Aldob  9.03E−178 0.365460648  9.03E−178 Abcd2  1.40E−177 0.285090597  1.40E−177 Gc  2.82E−177 0.259816642  2.82E−177 Abcb4  3.66E−176 0.494736917  3.66E−176 mt-Co3  4.34E−176 −1.167027737  4.34E−176 Ugt2b5 NA −0.603351248  9.60E−175 Slc27a2  1.69E−174 0.385256962  1.69E−174 Ccl6 NA 0.78914235  1.24E−171 St3gal5  1.06E−170 0.607639775  1.06E−170 Hbb-bt NA 1.430134393  2.56E−170 Reep6  2.74E−169 0.514272451  2.74E−169 Slc16a6 NA 0.911357108  4.06E−168 Ttc36  1.00E−167 −0.660645659  1.00E−167 Adh1 NA −1.255028206  1.90E−167 Gsta3 NA −0.806290466  2.44E−166 Cvp2e1 NA −2.318570161  4.79E−166 Plin2 NA 1.461295758  8.58E−163 Il1r1 NA 1.244999819  1.47E−162 F2  3.99E−160 0.32133198  3.99E−160 Decr1  4.55E−160 0.466364339  4.55E−160 Actb 8.47E−52 1.059835055  6.06E−159 Slc25a47  1.45E−158 0.502661475  1.45E−158 Srgn NA 0.934067453  5.07E−158 Pabpc1  1.11E−157 0.494914201  1.11E−157 Cyp2d9 NA −0.640698605  3.96E−157 Hyou1 NA 0.846484822  1.62E−156 Lcat  8.53E−155 0.436082968  8.53E−155 Grn  1.07E−154 0.540768685  1.07E−154 Hsd3b5  1.41E−154 −1.069520224  1.41E−154 Ube2r2  1.35E−153 0.46659877  1.35E−153 Hamp NA −1.02112368  2.59E−153 Apoa5  8.39E−153 0.323188383  8.39E−153 Cdkn1a NA 1.2152557  2.99E−152 Serpina1c NA −0.402626732  7.17E−151 Gstp1  1.88E−150 −0.855831436  1.88E−150 Tubb6 NA 0.576687679  6.13E−150 Apoc4 NA −1.002265767  9.54E−150 Nid1 NA 0.342599117  1.04E−149 Calr NA 0.555145472  1.67E−148 Klf6 NA 0.732407935  1.50E−147 Cers6 NA 0.532818648  8.16E−146 Hmgcl  1.74E−145 0.473794522  1.74E−145 Aldh9a1  1.28E−144 0.415934269  1.28E−144 Txnrd1 NA 1.443578942  1.43E−144 Il1b NA 0.742893545  1.02E−143 Hspa8  1.80E−143 0.420379148  1.80E−143 Psat1 NA 0.301248562  8.43E−143 Gm23935  3.70E−142 1  3.70E−142 Tmbim6  4.11E−142 0.338652766  4.11E−142 Rgn NA −1.573093006  9.97E−141 Amy1  1.36E−140 0.432738347  1.36E−140 Uqcrq NA −0.88665513  1.50E−140 Scd1  5.06E−126 0.726687286  2.08E−139 Itih4 NA 0.525074867  4.26E−137 Gyk  8.15E−137 0.402444184  8.15E−137 Hp NA 0.431328341  8.95E−137 Chka NA 1.375010255  2.35E−136 Pdia3 NA 0.593769188  7.36E−136 Decr2  6.71E−135 0.418851877  6.71E−135 Cyp3a25  1.19E−134 −0.386094858  1.19E−134 Serping1  1.56E−134 0.41280952  1.56E−134 Wbp1l  4.08E−134 0.553507326  4.08E−134 Hsp90b1 NA 0.534208217  6.37E−134 Gnmt NA −0.46036106  1.33E−133 Atp5k  1.43E−133 −0.47725773  1.43E−133 2010003K11Rik NA 0.588354735  2.61E−131 Serpina3m  1.04E−130 0.967441963  1.04E−130 Slco1b2 1.55E−55 −1.087378176  3.68E−129 Lipa  3.72E−129 0.41833763  3.72E−129 Mup20  3.88E−128 −0.476207303  3.88E−128 Rgs16  5.95E−128 0.322559157  5.95E−128 Bhmt NA −0.520184894  1.20E−127 Vtn  2.90E−126 0.333811366  2.90E−126 Plin5  1.22E−125 0.352087102  1.22E−125 C3  1.44E−100 0.449521065  1.23E−125 Agpat6  2.13E−125 0.396260224  2.13E−125 Acat1  2.19E−125 0.368871999  2.19E−125 Ets2 NA 0.695623802  2.30E−125 Mup4  9.25E−125 −1.087038527  9.25E−125 Atp5h  1.41E−124 −0.6398091  1.41E−124 Car3  4.54E−111 −1.036093133  1.61E−124 Acbd5  5.03E−124 −0.3952179  5.03E−124 Nr1i3  2.82E−123 0.425883248  2.82E−123 Crat  3.69E−123 0.255626614  3.69E−123 Slc27a5  4.04E−123 0.336994904  4.04E−123 Oaf  1.03E−122 −0.7328674  1.03E−122 Cyp3a11  2.07E−107 −0.423130745  1.05E−122 Krt18 NA 1.257881489  3.97E−121 Elovl3 5.92E−91 −0.675967012  6.30E−121 Cox5a  6.48E−121 0.40236048  6.48E−121 Ahcy NA −0.562968597  6.43E−120 Sdhc  1.27E−118 0.394392518  1.27E−118 Gstt3  3.52E−118 0.350739865  3.52E−118 Asl  3.45E−117 0.558638879  3.45E−117 Atp5b  3.82E−117 0.291727476  3.82E−117 C9  4.51E−117 −0.427055258  4.51E−117 Cyp2b10 NA −1.164490931  9.40E−117 1100001G20Rik NA −0.851607217  1.14E−116 Slc25a20  4.01E−116 0.380017899  4.01E−116 Hba-a1 NA 0.734957385  2.58E−115 Ildr2  2.61E−115 0.267607713  2.61E−115 Ppara  4.20E−115 0.35885744  4.20E−115 Dusp5 NA 0.296374788  1.01E−114 Mup8  1.23E−114 −0.79575704  1.23E−114 P4hb 1.25E−84 0.405223744  2.27E−113 2810007J24Rik NA −0.914301122  6.76E−113 Rpl38  9.16E−113 0.254329206  9.16E−113 Tgoln1  1.14E−112 0.38833408  1.14E−112 Cox4i1 NA −0.515989169  4.62E−112 Brap  5.49E−112 0.349229859  5.49E−112 Cox8a  5.50E−112 0.44171223  5.50E−112 Bfar  4.46E−110 0.290332897  4.46E−110 D17Wsu92e  5.84E−110 0.371951808  5.84E−110 Glud1 NA 0.451048591  6.55E−110 Slc40a1  1.18E−109 0.466969696  1.18E−109 Ephx2  3.91E−109 −0.369303553  3.91E−109 Bnip3  1.26E−108 0.403206563  1.26E−108 Rnase4 NA −1.049196753  1.89E−107 Dhcr24  3.03E−107 0.423756767  3.03E−107 Myh9 NA 1.160233135  3.10E−107 Acad11  7.32E−107 0.357135026  7.32E−107 Fn1 3.08E−64 0.699634526  1.87E−106 Mia3  3.36E−106 0.364623797  3.36E−106 Gm6484  3.87E−106 0.304268201  3.87E−106 Zfp91  6.43E−106 0.370686172  6.43E−106 Gm2a  1.13E−105 0.383109253  1.13E−105 Sec14l2  4.44E−105 −0.789737513  4.44E−105 Cyp2a12  7.61E−104 0.374332361  7.61E−104 Krt8 NA 1.195874806  1.04E−103 Lpin2  1.43E−103 0.686687426  1.43E−103 Clec4f NA 1.108180782  2.17E−103 Cidec NA 0.299384206  1.71E−102 B2m NA −0.417973886  1.86E−102 Slc4a4  2.71E−102 0.420259653  2.71E−102 Sh3glb1  3.84E−102 0.326006747  3.84E−102 Tmed5  5.01E−102 0.401633325  5.01E−102 Serpinf1  5.71E−102 0.319550979  5.71E−102 0610005C13Rik  2.41E−101 −0.425135941  2.41E−101 Rpl4  2.66E−101 0.283935593  2.66E−101 Dbi NA −0.716365271  3.56E−101 Apoa4 8.65E−87 1.367998503  8.56E−101 Acot12  1.49E−100 0.307840041  1.49E−100 Acot1  1.49E−100 0.307840041  1.49E−100 Scp2  3.33E−100 −0.519124916  3.33E−100 Uroc1  3.97E−100 0.416226092  3.97E−100 Bcl2l1 NA 0.775118224 1.02E−99 Mmp8 NA 0.359005863 1.02E−99 Cyp2c29 NA −1.149629979 1.97E−99 Snord13 2.42E−99 0.261078586 2.42E−99 Acadl 4.33E−99 0.316216015 4.33E−99 Cpt1a 2.13E−98 0.372935212 2.13E−98 Akr1d1 2.99E−98 0.361037667 2.99E−98 Cyp7b1 3.09E−98 −0.65802273 3.09E−98 Mgll 5.21E−98 0.333899751 5.21E−98 Sult1d1 1.12E−97 0.45987026 1.12E−97 Slc25a10 1.85E−97 0.343272504 1.85E−97 Vnn3 1.94E−97 0.276458974 1.94E−97 Pigr 2.38E−97 0.386842112 2.38E−97 Pzp NA 0.41600896 3.34E−97 Serpina1b NA −0.301770579 4.66E−97 Tmem205 NA −0.774742732 1.05E−96 Mup14 2.64E−96 −0.760766854 2.64E−96 Ces1b 3.47E−96 0.372958858 3.47E−96 C8g NA −0.654510262 4.13E−96 Cd14 NA 0.362089625 2.79E−95 Mtdh 2.84E−95 0.30466184 2.84E−95 Hdlbp NA 0.565147241 5.10E−95 Tmbim4 5.14E−95 0.32269634 5.14E−95 Saa2 6.06E−64 0.964488054 8.96E−95 Abcc3 9.62E−95 0.363799323 9.62E−95 Serpina10 NA 0.565046404 8.21E−94 Cyp2c44 1.11E−93 0.385935584 1.11E−93 Rcan1 NA 0.707283787 1.24E−93 Arrdc3 NA 0.526871989 2.74E−93 Hsd3b7 1.78E−61 −1.0059958 3.79E−93 Rell1 NA 0.591181865 1.02E−92 Prdx1 1.10E−92 −0.529229113 1.10E−92 Fah 1.16E−92 0.302494707 1.16E−92 Chpt1 1.36E−92 0.35662056 1.36E−92 Mthfd2 NA 0.262448025 1.46E−92 Gfra1 2.65E−92 0.386382804 2.65E−92 Retnlg NA 0.375148336 4.49E−92 Pbld1 4.53E−92 −0.442542986 4.53E−92 Creld2 NA 0.608652695 1.18E−91 Aplp2 1.48E−91 0.33938781 1.48E−91 Lifr 2.60E−91 −0.626180925 2.60E−91 Ces1d 7.83E−69 −0.428906017 8.07E−91 D10Wsu102e NA 0.58780186 2.09E−90 Camk2n1 4.24E−90 0.250109512 4.24E−90 Rps27l NA −0.865927484 5.43E−90 Bche 7.85E−90 0.313419985 7.85E−90 Itih3 NA 0.546240791 1.11E−89 Plscr1 NA 0.444489505 2.65E−89 Gm24270 NA 0.26796863 3.13E−89 Tmem56 6.36E−89 1 6.36E−89 Rdx 1.02E−88 0.373557306 1.02E−88 Abca6 1.30E−88 0.33284944 1.30E−88 Gpld1 1.61E−88 0.328106789 1.61E−88 Lrrc58 NA 1.001096085 3.66E−88 Hba-a2 NA 0.553546734 5.15E−88 Fxyd5 NA 0.274279595 7.76E−88 Cyp8b1 3.14E−45 −0.889229825 8.76E−88 Cox6a1 1.78E−87 −0.48722865 1.78E−87 Ctage5 2.41E−87 0.328678207 2.41E−87 Pex11a 3.08E−87 0.350827626 3.08E−87 Ass1 5.20E−87 −0.314400604 5.20E−87 Mttp 1.44E−86 0.311504107 1.44E−86 Eci2 1.53E−86 0.311004843 1.53E−86 Prodh2 1.88E−86 0.345294809 1.88E−86 Gadd45g NA −0.614019025 7.38E−86 Psen2 NA −0.947373772 1.77E−85 Creg1 2.77E−85 0.276773054 2.77E−85 BC025446 4.26E−85 0.29422883 4.26E−85 Serpina3n 9.93E−85 0.848313239 9.93E−85 Slc10a1 1.24E−84 −0.325757408 1.24E−84 Met 1.73E−84 0.288332662 1.73E−84 Mettl7b 1.73E−84 −0.452656656 1.73E−84 Pck1 1.26E−61 −0.652190949 1.90E−84 Oat NA −1.224853019 6.25E−84 Pcbp2 1.30E−83 0.310347013 1.30E−83 Atf5 1.74E−83 0.329004772 1.74E−83 Tyrobp NA 0.466551501 1.85E−83 C230081A13Rik NA 0.426976229 3.42E−83 Hnf4a 3.56E−83 0.879108718 3.56E−83 Atxn7l3b 6.16E−83 0.306239775 6.16E−83 G0s2 8.79E−83 0.346452213 8.79E−83 F10 9.43E−83 0.279095541 9.43E−83 Pla2g7 NA 0.282344956 9.47E−83 Rplp0 1.83E−82 −0.430901519 1.83E−82 Gcdh 4.27E−82 −0.300320098 4.27E−82 Creb3l3 5.52E−82 0.275700825 5.52E−82 Ssr3 NA 0.521769281 5.71E−82 Eef1a1 NA 0.439251983 2.20E−81 Slc39a14 NA 1.012749203 2.25E−81 Man2a1 2.32E−81 0.497115325 2.32E−81 Cox6c NA −0.844280539 3.24E−81 Il1r2 NA 0.323447978 5.62E−81 Actn4 7.73E−81 0.312388865 7.73E−81 Ptprc NA 0.416505491 1.46E−80 Eif5 1.55E−80 0.576301866 1.55E−80 Slc25a13 1.65E−80 0.285473174 1.65E−80 Hint1 NA −0.673880575 1.71E−80 Echs1 3.04E−80 −0.331606352 3.04E−80 Aco2 5.35E−80 0.285855791 5.35E−80 Pnpla8 6.50E−80 0.295631611 6.50E−80 C1qb NA 0.681679654 1.02E−79 Hsd17b10 1.43E−79 −0.377206484 1.43E−79 Egfr 5.82E−71 0.504957782 1.72E−79 Cyp2a5 NA −1.498910166 3.74E−79 Asgr2 6.28E−79 0.306445529 6.28E−79 Tmsb4x NA 0.780616209 7.99E−79 Hsd17b13 8.89E−79 0.680828119 8.89E−79 Dennd5b 1.08E−78 0.293458876 1.08E−78 Ctsh 1.35E−78 0.32445036 1.35E−78 Igf1 1.83E−78 0.295791825 1.83E−78 Apc NA 0.606730845 2.16E−78 Apcs NA 0.75840106 2.16E−78 Ctss NA 0.764167083 2.26E−78 Cyp2d26 2.76E−78 0.259136874 2.76E−78 Tcea3 2.91E−78 −0.355007815 2.91E−78 Klf9 3.25E−78 0.293415875 3.25E−78 Orm1 1.56E−69 0.365144434 4.87E−78 Clec4d NA 0.26359638 5.98E−78 Mlycd 7.66E−78 0.313046697 7.66E−78 Maob 2.74E−77 0.32037326 2.74E−77 Kif1b 2.75E−77 0.371764707 2.75E−77 Insig2 5.68E−77 0.669991504 5.68E−77 Ces3a NA −0.52533635 5.80E−77 G6pc NA −0.960058274 1.00E−76 Cth NA −0.510899065 1.34E−76 Pgrmc1 NA 0.350152674 1.59E−76 Ugt2b1 NA −0.776816931 2.28E−76 Mup13 6.20E−45 −0.77574306 2.45E−76 Gabarap 3.49E−76 −0.442546824 3.49E−76 Arhgap5 4.88E−76 0.295235575 4.88E−76 Cyp1a2 2.09E−66 −0.993935836 1.08E−75 Hgd NA −0.758572265 1.96E−75 Adck3 NA −0.87611538 2.27E−75 Abhd14b 2.40E−75 −0.39366782 2.40E−75 Serinc3 4.67E−75 0.35928911 4.67E−75 Gltscr2 5.18E−75 0.255310647 5.18E−75 Vcam1 NA 0.457401491 6.00E−75 Urah NA −0.764109132 1.55E−74 Sord 1.84E−74 −0.383628337 1.84E−74 Agpat9 NA 0.327040595 2.14E−74 Etnppl 3.56E−74 0.496712405 3.56E−74 Por 1.06E−73 0.335963246 1.06E−73 Rsp14 1.07E−73 −0.402093042 1.07E−73 Lamp1 1.16E−73 0.268283663 1.16E−73 Plek NA 0.308857869 1.40E−73 Ctsa 2.08E−73 0.252009224 2.08E−73 Mrap NA 0.884099926 2.65E−73 Dnajc3 NA 0.45638751 2.66E−73 Adamts1 NA 0.282556845 8.88E−73 Hadh 9.69E−73 0.288772268 9.69E−73 C8b 1.12E−72 −0.360171247 1.12E−72 Csad NA −0.559786018 1.92E−72 Nr1d2 NA 0.430636791 2.60E−72 Sod1 NA −0.439319795 3.30E−72 Ech1 1.35E−56 −0.429132615 5.62E−72 Ddb1 1.19E−71 0.277809186 1.19E−71 Kng1 NA 0.265777676 1.32E−71 Shmt1 8.69E−71 −0.393237106 8.69E−71 Acsl1 1.12E−70 −0.370316988 1.12E−70 C4b 3.16E−70 0.283273876 3.16E−70 Gcnt2 NA 0.537509676 4.50E−70 Csf1r NA 0.704458586 4.70E−70 Ggnbp2 9.71E−70 0.272604502 9.71E−70 Nfe2l1 1.23E−69 0.27034473 1.23E−69 Tomm70a 1.99E−69 0.268786029 1.99E−69 Steap4 NA 0.475973731 6.59E−69 Atp2a2 7.58E−69 0.494962728 7.58E−69 Cd1d1 7.99E−69 0.291156805 7.99E−69 Comt 1.01E−68 −0.368377448 1.01E−68 Sec62 1.84E−68 0.251575572 1.84E−68 Cxcr2 NA 0.40229963 2.86E−68 Slc7a2 3.47E−68 0.352564931 3.47E−68 C130074G19Rik 4.06E−68 −0.356338948 4.06E−68 Apob NA 0.580156235 4.36E−68 Furin 8.30E−68 0.405633752 8.30E−68 Cxcl1 9.38E−68 0.449766784 9.38E−68 Cxcl12 9.38E−68 −0.305838679 9.38E−68 Khk 1.03E−67 −0.491453217 1.03E−67 Ei24 1.18E−67 0.257327011 1.18E−67 Cd163 NA 0.440845529 1.51E−67 Trp53inp1 NA 1.008414088 1.52E−67 Eif4g2 NA 0.559692663 1.62E−67 Gys2 1.83E−67 0.274401611 1.83E−67 Dmgdh 2.36E−67 0.265846058 2.36E−67 Tob1 3.20E−67 −0.338705886 3.20E−67 Ubc NA −0.661839716 4.04E−67 Cbr1 7.07E−67 0.284717454 7.07E−67 Pon1 NA −0.685751275 1.66E−66 Suds3 1.93E−66 0.25388963 1.93E−66 1700017B05Rik NA 0.330656885 2.40E−66 Ugp2 6.86E−66 0.297335445 6.86E−66 Iigp1 NA 0.768753667 7.59E−66 Nop58 NA 0.663449653 2.13E−65 Padi3 NA 0.295682522 2.63E−65 Pipox 2.97E−65 0.272543042 2.97E−65 Ndufa4 NA −0.683126695 3.70E−65 Gsta1 NA 0.407606856 7.64E−65 F9 8.09E−65 0.256805166 8.09E−65 B4galt5 NA 0.476306558 1.12E−64 F12 2.98E−64 0.256737037 2.98E−64 Fcgrt 4.12E−64 −0.269314211 4.12E−64 Fmo5 4.71E−64 0.286219883 4.71E−64 Rnf144a NA 0.313046134 7.90E−64 Ugt2b36 NA −0.583431487 1.36E−63 Sardh 1.48E−63 0.269183147 1.48E−63 Iqgap1 NA 0.45544473 1.82E−63 Creb3l2 NA 0.427180051 1.91E−63 Slc22a1 NA −0.797941816 2.27E−63 Lyz2 NA 0.732183369 2.49E−63 Bach1 NA 0.832333098 2.51E−63 Lpgat1 3.53E−63 0.595219291 3.53E−63 Atp1a1 3.57E−63 0.419079339 3.57E−63 Fam134b NA 0.893562894 5.02E−63 Hsd17b4 6.45E−63 0.253232967 6.45E−63 Gabarapl1 9.11E−63 0.260716513 9.11E−63 Cd5l NA 0.693485826 1.08E−62 Elovl2 NA 0.45224665 1.22E−62 Lrg1 NA 0.490792829 1.37E−62 Hgfac 1.72E−62 0.252189991 1.72E−62 Atp5d 2.36E−62 0.250062798 2.36E−62 Efhd2 NA 0.583831769 3.26E−62 Pcbd1 NA −0.687761883 6.29E−62 mmu-mir-6240 NA 1.101237189 9.82E−62 Hagh NA −0.674009711 1.62E−61 Hsd3b3 3.00E−20 −0.779501123 1.98E−61 Tmem106b 2.12E−61 0.280204492 2.12E−61 Ctsd 4.43E−61 0.257862212 4.43E−61 Cd44 NA 0.303745221 5.24E−61 Rdh16 5.97E−61 0.269182372 5.97E−61 Cyp2c70 6.16E−61 −0.551134023 6.16E−61 Thrsp 6.83E−61 −0.724961807 6.83E−61 Hadha 7.14E−61 0.250937029 7.14E−61 Sdhd 8.20E−61 −0.335261252 8.20E−61 Mbl1 NA −0.713006005 1.05E−60 Ddt NA −0.522221147 1.33E−60 Eif1a NA 0.795281298 1.80E−60 Alb NA 0.420298986 1.86E−60 Pdia4 NA 0.488166898 1.94E−60 F5 3.21E−60 0.300566587 3.21E−60 Laptm5 NA 0.338180771 3.31E−60 Slc2a2 5.54E−60 −0.312348392 5.54E−60 Sfxn1 7.27E−60 0.304885886 7.27E−60 Epas1 NA 0.775763153 7.57E−60 Alas1 NA −0.489837477 8.49E−60 Cd97 NA 0.345774315 1.02E−59 Hacl1 NA −0.706897734 1.20E−59 Oaz1 1.75E−59 −0.418528822 1.75E−59 Hpd NA −0.518180386 2.47E−59 Cd74 NA 0.453937562 3.15E−59 Aldh3a2 1.43E−09 −0.834229334 3.38E−59 Gclm 3.66E−59 0.269864161 3.66E−59 Serpina3c 8.19E−59 −0.472511045 8.19E−59 Sdc4 NA 0.619597869 9.47E−59 Ubxn4 1.03E−58 0.250313647 1.03E−58 Ptms 1.24E−58 0.267838974 1.24E−58 Wfdc17 NA 0.486653465 2.57E−58 Gsta2 2.63E−58 0.252161786 2.63E−58 1110008F13Rik NA −0.455270589 4.13E−58 Fkbp5 NA 0.516128063 1.44E−57 mt-Nd6 NA −0.477851134 1.67E−57 Kctd3 NA 0.260833465 2.11E−57 Sec61a1 2.23E−57 0.313944633 2.23E−57 Ddx21 NA 0.73138069 2.25E−57 Pdcd4 NA 0.48815423 3.64E−57 Upb1 7.94E−57 −0.418695518 7.94E−57 Cyp2c37 NA −0.886903784 9.93E−57 Cd53 NA 0.265579528 1.37E−56 Park7 1.55E−56 −0.260230015 1.55E−56 Hic2 NA 0.289767391 2.03E−56 Sat1 NA 0.68869896 2.31E−56 Btg2 NA 0.832086378 3.81E−56 Usmg5 4.55E−56 −0.43049483 4.55E−56 Rgs2 NA 0.395729601 7.50E−56 Chchd2 NA −0.552503492 7.88E−56 Slc37a4 1.06E−55 0.268318739 1.06E−55 Inmt 7.77E−21 −0.731016404 1.21E−55 Cyp2d10 NA −0.323151441 1.31E−55 Itgb2 NA 0.272302012 1.36E−55 Cps1 NA 0.32450205 1.45E−55 Keg1 2.32E−52 −0.824548137 1.46E−55 C1qc NA 0.586092716 2.05E−55 AI182371 NA 0.447854829 2.62E−55 Rock2 NA 0.594094466 2.90E−55 Sqstm1 NA 0.743150456 4.59E−55 Fndc3b NA 0.409645989 4.69E−55 Uox NA −0.553115511 6.13E−55 Gulo NA −0.801665727 6.80E−55 mt-Tq NA 0.287889985 7.13E−55 C8a 7.61E−55 0.333650228 7.61E−55 Tiparp NA 0.545567123 8.73E−55 Fcgr3 NA 0.308247077 1.21E−54 Uqcr11 NA −0.603079991 1.37E−54 Atp5e NA −0.650247857 2.15E−54 Tram1 NA 0.411080257 2.39E−54 Prg4 NA 0.430643187 3.20E−54 Upp2 NA −0.69025963 3.29E−54 H2-Ab1 NA 0.460956687 3.42E−54 Gm26917 NA 0.823736053 5.26E−54 Aldh8a1 NA −0.683676902 5.66E−54 Glyat NA −0.647687911 1.11E−53 Msrb1 NA −0.59903268 1.16E−53 Manf NA 0.468881688 1.60E−53 Spred1 NA 0.388422711 1.65E−53 Orm2 NA 0.271460545 2.71E−53 Sparcl1 3.40E−53 −0.253616986 3.40E−53 Cat NA 0.262624418 7.22E−53 Ndufb11 4.56E−22 −0.509671057 8.28E−53 C1qa NA 0.514846404 1.51E−52 Cldn14 NA 0.364540783 1.86E−52 Heatr1 NA 0.406005371 2.23E−52 Calm1 NA 0.413146039 2.28E−52 Insig1 NA 0.465534816 3.03E−52 Cfh 2.09E−34 0.400919606 3.24E−52 Ppp2r5a 7.14E−52 −0.260504538 7.14E−52 Hc NA 0.367935082 1.11E−51 Hebp1 NA −0.635432267 1.18E−51 Ces1e 2.36E−51 0.265618893 2.36E−51 Cox7b NA −0.642240776 3.42E−51 Abhd2 NA 0.484366625 1.13E−50 Picalm NA 0.754529703 1.39E−50 Igfbp1 NA 1.058689301 1.68E−50 Haao NA −0.591181029 2.08E−50 Canx NA 0.343383207 2.09E−50 Cebpb NA −0.471579534 2.38E−50 Stat3 NA 0.715400235 2.74E−50 Fgl2 NA 0.281793883 2.86E−50 AA474408 NA 0.43640813 3.01E−50 Lyst NA 0.409280587 8.39E−50 Myo1e NA 0.614341001 9.34E−50 Tmem87b NA 0.434399269 1.07E−49 Slc10a2 NA 0.299006165 2.04E−49 Gnl3 NA 0.575970422 2.63E−49 Lcn2 NA 0.412194792 2.72E−49 Jmjd1c NA 0.636619821 3.43E−49 Cox7a2 NA −0.650338386 2.00E−48 Cltc NA 0.784985399 3.05E−48 Rarres2 NA −0.552194576 3.29E−48 Sc5d NA −0.500900917 3.57E−48 Ndufa6 NA −0.613649978 4.43E−48 2-Mar NA −0.55994977 4.66E−48 Hspa13 NA 0.354844877 7.52E−48 Btg1 NA 0.458007046 1.02E−47 Pah NA −0.52207695 1.25E−47 Leap2 NA −0.671300937 1.25E−47 Cytip NA 0.267599208 1.05E−46 Clpx NA −0.404735614 1.07E−46 Sdc3 NA 0.359804895 1.11E−46 mt-Tm NA 0.284684642 1.20E−46 Gm24187 NA 0.431940663 1.37E−46 Stk40 NA 0.536418312 2.15E−46 Cyp2c50 NA −0.661823297 2.92E−46 Cfp NA 0.356178244 6.11E−46 Dot1l NA 0.397036294 7.81E−46 Saa4 NA −0.571021905 1.16E−45 Atp8b1 NA 0.362807422 1.42E−45 Mdn1 NA 0.317989246 1.53E−45 Ndufb2 1.66E−45 −0.577154458 1.66E−45 Hsd17b2 2.36E−31 −0.595878526 3.18E−45 H2-Eb1 NA 0.327872672 3.30E−45 Cxadr NA 0.698450944 4.99E−45 Gstm3 5.34E−45 −0.598573335 5.34E−45 Cpb2 NA 0.322179327 5.47E−45 Spcs3 NA 0.394206972 9.16E−45 Cd302 NA −0.549925078 1.10E−44 Plg NA 0.261736006 1.34E−44 Lactb2 NA −0.596505052 1.72E−44 Tsr1 NA 0.360287403 2.32E−44 Igfbp2 NA −0.345087789 4.02E−44 Rps2 5.09E−44 −0.387862655 5.09E−44 Dgkd NA 0.370844881 1.62E−43 Cml1 NA −0.61424052 1.70E−43 Sorl1 NA 0.306655621 1.87E−43 Tra2a NA 0.712328169 2.35E−43 Dcxr NA −0.440851615 2.61E−43 Aadac NA −0.619958028 4.18E−43 Ppib 6.71E−21 −0.589699514 1.14E−42 Lect2 NA −0.626967771 1.41E−42 Tlcd2 NA −0.594498821 1.60E−42 Lpin1 1.78E−42 0.277494868 1.78E−42 Ttc39c 2.88E−40 −0.636274928 2.03E−42 Tacc2 NA 0.329332932 3.95E−42 Gchfr NA −0.554783473 4.46E−42 Tmed7 NA 0.386771014 6.68E−42 Usp9x NA 0.407617259 9.98E−42 Aldh1a1 NA −0.478797447 1.02E−41 Sdad1 NA 0.312421192 1.30E−41 Fdx1 NA −0.623439092 1.55E−41 Eef2 NA 0.525855561 2.71E−41 Gstz1 NA −0.464086834 2.81E−41 Ptpn1 NA 0.41633121 3.51E−41 Tnfrsf1a NA 0.599573483 3.86E−41 Rad54l2 NA 0.388705156 4.52E−41 Il13ra1 NA 0.30296595 4.97E−41 Pemt NA −0.551184095 7.86E−41 Acss2 3.19E−11 −0.620071374 8.55E−41 1-Mar NA −0.477762617 9.43E−41 Ddx3x NA 0.656890035 1.07E−40 Hs3st3b1 NA 0.343007923 1.60E−40 Acox1 NA 0.275171428 1.78E−40 Atp5j2 NA −0.51308051 3.32E−40 8430408G22Rik NA −0.50210224 4.85E−40 Ndufb9 NA −0.503828812 5.48E−40 Hif1a NA 0.516911277 5.71E−40 Hes6 1.91E−06 −0.561302344 5.81E−40 Tsku NA 0.36762763 6.05E−40 Dnajc12 NA 0.322094554 1.14E−39 Eaf1 NA 0.521796522 1.19E−39 Qdpr NA −0.52357376 1.45E−39 Atp5f1 NA −0.517061165 2.05E−39 Gm4076 2.57E−39 −0.325469418 2.57E−39 Uso1 NA 0.388069473 3.58E−39 Maff NA 0.355300257 4.89E−39 Qsox1 NA 0.342352868 9.20E−39 Adh4 NA −0.526868306 1.92E−38 Chic2 NA 0.419790279 2.33E−38 Eef1b2 2.36E−38 −0.317323205 2.36E−38 Adh5 NA −0.491433382 2.88E−38 Itih2 NA 0.501091194 3.43E−38 Gjb2 NA 0.60822545 3.74E−38 Fabp2 NA −0.615569339 4.18E−38 Slc20a1 NA 0.357248475 6.66E−38 Slc3a1 NA 0.340997565 7.10E−38 Mup2 8.16E−38 1 8.16E−38 Abca1 NA 0.724477701 8.81E−38 Ndufa7 NA −0.555912274 1.32E−37 Lgmn NA 0.484586871 1.80E−37 Gamt NA −0.560282685 2.41E−37 Bcl3 NA 0.289017645 3.63E−37 Hint2 NA −0.424321102 6.90E−37 Mpc2 NA −0.482839417 7.20E−37 Atxn1 NA 0.304881734 9.14E−37 Cyp2c54 9.37E−37 −0.39493764 9.37E−37 Fos NA 0.432003299 1.43E−36 St3gal1 NA 0.528739882 1.81E−36 Msn NA 0.260172491 1.86E−36 Sds 3.53E−09 −0.407006722 2.82E−36 Rpn1 NA 0.41242919 5.16E−36 Ucp2 NA 0.261164666 8.74E−36 Tcerg1 NA 0.357549618 1.14E−35 Akr1c20 NA −0.554152364 1.48E−35 Dst NA 0.510971252 1.75E−35 Dstn NA 0.324301394 1.75E−35 S100a1 NA −0.376186192 1.76E−35 Sar1b NA −0.317607513 1.79E−35 Crp NA −0.506869364 2.22E−35 Pfkfb2 NA 0.290016291 2.41E−35 Gm4952 NA −0.49867829 4.03E−35 Ndufb6 NA −0.507682563 4.30E−35 Vsig4 NA 0.483290635 4.48E−35 Hao1 NA 0.32303248 4.98E−35 Tubb2a NA 0.749433744 5.17E−35 Arl4d NA −0.507228317 6.71E−35 mmu-mir-6236 2.00E−10 0.787474192 7.24E−35 Apobec1 NA 0.305082858 9.49E−35 Akr1c14 NA −0.518570798 1.08E−34 Tmem30a NA 0.332760453 1.95E−34 Cfhr2 2.09E−34 −0.44846316 2.09E−34 Slc41a2 NA 0.278262888 2.13E−34 Ipo7 NA 0.324580152 2.19E−34 Tsc22d2 NA 0.391059638 2.43E−34 Cyb5r3 NA 0.339033056 3.10E−34 Apol7a NA −0.492294435 3.11E−34 Fxyd1 NA −0.479908398 3.83E−34 Cox5b NA −0.498783616 4.68E−34 Rplp1 NA −0.504662964 4.91E−34 Ugdh NA 0.633076584 5.17E−34 H2-Aa NA 0.327934784 6.84E−34 H3f3b NA 0.702914634 7.03E−34 Ppan NA 0.272410087 7.48E−34 Ugt2a3 NA −0.333441405 8.21E−34 Xbp1 NA 0.603165814 9.59E−34 Tjp2 NA 0.411461753 1.10E−33 Tatdn2 NA 0.373296072 1.22E−33 Hibadh NA −0.499409672 1.26E−33 Pten NA 0.355902258 1.92E−33 Ctsl NA 0.530101805 1.93E−33 Hspb8 NA 0.633933124 2.00E−33 Atp5j NA −0.48373528 3.59E−33 Usp4 NA 0.324732042 4.02E−33 Nolc1 NA 0.47222269 4.11E−33 Ier5 NA 0.288994609 4.64E−33 Lonp2 NA −0.467365882 5.23E−33 Rpl32 8.16E−20 −0.532218378 1.10E−32 Rrbp1 NA 0.306944991 1.11E−32 Dio1 NA −0.545283744 1.11E−32 Tmem256 NA −0.518510202 1.19E−32 Pdia6 NA −0.389966782 1.21E−32 Ssr1 NA 0.327818552 1.30E−32 Gm5096 NA −0.363089147 1.95E−32 Mcm10 NA −0.487427572 2.29E−32 Ibtk NA 0.331106132 4.10E−32 Nit2 NA −0.485940613 4.49E−32 Ppm1k NA −0.558394496 6.56E−32 Son NA 0.542911509 7.13E−32 Adh6-ps1 NA −0.418504072 9.38E−32 Selenbp1 NA −0.493707332 9.52E−32 Uggt1 NA 0.284457726 1.12E−31 Efna1 NA 0.336097237 1.73E−31 Ssr4 NA −0.507577243 1.87E−31 Ndufs6 NA −0.537929827 2.00E−31 1600014C10Rik NA −0.498182953 2.43E−31 Gas5 NA −0.336153154 2.74E−31 Nop56 NA 0.265670844 2.87E−31 Etfb NA −0.365490277 4.01E−31 Dusp16 NA 0.46051738 4.23E−31 Rora NA 0.644354953 5.02E−31 Nedd4 NA 0.377388355 6.69E−31 Epb4.1 NA 0.562789274 1.67E−30 Csde1 NA 0.326883793 1.68E−30 Ranbp2 NA 0.598499679 2.18E−30 Kmo NA −0.384440188 3.26E−30 Ndufa13 NA −0.43876131 3.68E−30 Rnd3 NA 0.36548808 3.93E−30 Prkd3 NA 0.366517526 3.93E−30 Nr5a2 NA 0.322039014 5.05E−30 Gm23388 NA 0.416208382 5.50E−30 Ddx5 NA 0.522944475 5.90E−30 Blvrb NA −0.545112721 6.23E−30 Lrp1 NA 0.505128824 6.85E−30 Cfi NA 0.251606433 7.20E−30 Mmp14 NA 0.288913135 7.66E−30 Plec NA 0.467512335 8.30E−30 Rab1 NA 0.352627435 1.03E−29 Jak1 NA 0.603850485 1.34E−29 Slco1a1 1.36E−29 −0.362843757 1.36E−29 Errfi1 NA 0.393680047 1.52E−29 Slc38a4 NA 0.263698621 2.48E−29 Uqcr10 NA −0.45190185 2.60E−29 Nab1 NA 0.33421071 3.00E−29 Il6st NA 0.333486533 3.02E−29 Mpc1 NA −0.281762702 3.39E−29 Cmah NA 0.361552447 5.19E−29 Calu NA 0.304112196 5.69E−29 Mlec NA 0.324558531 7.94E−29 Tm4sf4 NA 0.512552747 1.16E−28 Hal 1.20E−28 0.280113531 1.20E−28 Cmbl NA −0.442706435 1.48E−28 Baz1a NA 0.259610685 1.78E−28 Ak3 NA 0.289040998 1.86E−28 Nrp1 NA 0.360791537 1.93E−28 Gpt2 NA 0.539114072 2.49E−28 Etf1 NA 0.559444816 2.60E−28 Hook1 NA 0.327423989 3.21E−28 Ndufb4 NA −0.453693039 3.64E−28 Lgr4 NA 0.268964381 9.73E−28 Lrrc59 NA 0.377173076 1.35E−27 Dkc1 NA 0.32575964 1.54E−27 Stard10 NA −0.338316568 1.68E−27 Hpx NA −0.303288229 1.79E−27 Etnk1 NA 0.352068809 1.82E−27 Agmat NA −0.471832829 2.33E−27 Stard4 NA 0.351527506 2.40E−27 Cyp39a1 NA 0.351128984 2.44E−27 Malat1 NA 0.920628097 2.62E−27 Dusp6 NA 0.59164596 2.71E−27 Ywhag NA 0.58241474 3.05E−27 Adipor2 NA −0.473791512 3.14E−27 Arcn1 NA 0.327775216 3.29E−27 Serp1 1.29E−19 0.312399212 3.50E−27 Ifitm3 4.18E−27 −0.425091425 4.18E−27 Ces3b 5.30E−27 −0.36637965 5.30E−27 Fcna NA 0.377428055 5.71E−27 App NA 0.361832458 6.12E−27 Cyp2c67 NA −0.463488581 1.02E−26 Lrrfip1 NA 0.445928709 1.19E−26 Dhrs3 NA −0.467621234 1.25E−26 Rpl36a1 NA −0.475541391 1.26E−26 Cml2 NA −0.397916138 1.85E−26 Ppp1r3b NA −0.402657788 2.29E−26 Eif4g1 NA 0.374860037 2.42E−26 Ptpn12 NA 0.33417878 5.69E−26 Pik3c2a NA 0.324870962 5.98E−26 Cyp4a12a 7.00E−24 −0.456827492 6.69E−26 Mug2 NA 0.370406564 6.96E−26 Lman1 NA 0.29860668 9.00E−26 Hspe1 1.46E−15 −0.480734946 9.37E−26 Mrpl14 NA −0.459040925 9.74E−26 Zfp683 NA −0.421689112 1.05E−25 Mak16 NA 0.317126116 1.09E−25 Acsl4 NA 0.314743242 1.14E−25 Copa NA 0.345094339 1.16E−25 mt-Atp6 3.18E−23 −0.573743033 1.31E−25 Uqcrh NA −0.429164519 1.41E−25 Slc38a3 NA −0.40978981 1.45E−25 Minos1 NA −0.455548025 2.00E−25 Ebpl NA −0.450334658 2.09E−25 Atox1 NA −0.446203219 2.48E−25 Tbc1d15 NA 0.488646353 2.52E−25 Aox3 NA −0.333319828 2.60E−25 Map2k3 NA 0.434654367 2.73E−25 Vkorc1 NA −0.404176916 3.15E−25 Cyp7a1 NA −0.431201844 3.19E−25 Trip12 NA 0.328304235 3.31E−25 Hpgd NA −0.387752401 3.49E−25 Lmo4 NA 0.320534245 3.97E−25 Cyb5b NA −0.423345561 4.82E−25 Klf15 NA −0.451831953 5.02E−25 Gnl2 NA 0.390473036 5.63E−25 3110043O21Rik NA 0.269386631 5.64E−25 Asgr1 NA −0.385655364 6.52E−25 Mtus1 NA 0.362060296 7.17E−25 Cyp2j5 NA −0.398305774 7.33E−25 Mup1 7.40E−25 1 7.40E−25 Prdx5 NA −0.28208825 8.22E−25 Chd1 NA 0.378763061 8.51E−25 Rarres1 1.03E−20 −0.455632451 8.53E−25 Sel1l NA 0.33595882 8.76E−25 Arl5a NA 0.264805346 1.52E−24 Mpeg1 NA 0.493478112 1.80E−24 Wdr43 NA 0.343830267 1.89E−24 Aff4 NA 0.616309327 1.96E−24 Timm13 NA −0.432961802 2.46E−24 1500017E21Rik NA −0.460997215 2.47E−24 Nop10 NA −0.291908137 2.62E−24 Serpina12 2.90E−24 −0.453399356 2.90E−24 Fam107b NA 0.463320341 2.90E−24 Cep85l NA 0.277893187 3.24E−24 Srpr NA 0.305179041 4.78E−24 Narf NA 0.262933124 6.15E−24 2410015M20Rik NA −0.402123463 6.84E−24 Gtpbp4 NA 0.482239467 6.84E−24 Prdx4 8.80E−10 −0.417588892 6.96E−24 Ccs NA −0.426694207 7.67E−24 Rps15 NA −0.455155041 7.79E−24 Tns1 NA 0.434939232 8.90E−24 Esd NA −0.280760023 9.90E−24 Ncl NA 0.48450982 1.05E−23 Stom NA 0.323229029 1.13E−23 Amacr NA −0.413582585 1.14E−23 Sco2 NA −0.292870629 1.32E−23 Glo1 NA −0.406574019 1.87E−23 Mcl1 NA 0.570934356 2.05E−23 Mybbp1a NA 0.431161557 2.11E−23 Nars NA 0.437769953 2.87E−23 Slc38a10 NA 0.285548034 2.98E−23 Gm10800 NA 0.562597493 3.19E−23 Stt3b NA 0.319405267 3.84E−23 Srp72 NA 0.310685136 5.31E−23 Prrc2c NA 0.439271845 6.04E−23 Zyx NA 0.298338034 6.24E−23 Sc4mol NA −0.326170476 6.26E−23 Mrp63 NA −0.442201567 7.79E−23 Arg1 NA 0.317948822 8.62E−23 Arhgef12 NA 0.590764816 8.83E−23 Acsm1 NA −0.369245009 9.63E−23 Mat2a NA 0.482570924 1.45E−22 Cars NA 0.315814572 1.93E−22 Rps9 NA −0.371793799 1.94E−22 Ell2 NA 0.417241283 2.55E−22 Gm24245 NA 0.546463773 3.25E−22 Rpl13a NA −0.381462137 3.58E−22 Bzw1 NA 0.294810535 3.59E−22 Grlf1 NA 0.295046691 3.99E−22 Bbox1 NA −0.408245616 4.17E−22 Map3k5 NA 0.33471162 4.76E−22 Pecr NA −0.398084036 4.93E−22 Ndufa3 NA −0.41160475 5.38E−22 Tmem14c NA −0.368514287 6.04E−22 Atp13a3 NA 0.394480252 6.61E−22 Pxk NA 0.281854648 6.95E−22 Rps18 NA −0.488540797 8.18E−22 Mrps24 NA −0.390380395 8.75E−22 Mtss1 NA 0.287581972 1.08E−21 Gjb1 NA −0.31656535 1.13E−21 Edem1 NA 0.286881059 1.13E−21 Spp2 NA −0.382096801 1.28E−21 Kif5b NA 0.50116686 1.57E−21 Acly NA 0.328803101 1.74E−21 Rpl13 NA −0.299693639 1.78E−21 1110001J03Rik NA −0.432785224 2.04E−21 Dync1li1 NA 0.262406206 2.23E−21 Ndufa2 NA −0.396473631 2.46E−21 Txndc5 NA 0.290124872 3.56E−21 Psme1 NA −0.394006165 3.58E−21 Ppp1r12a NA 0.356295305 3.60E−21 Bphl NA −0.40747923 5.02E−21 Trf NA −0.261883505 5.32E−21 Cyp2c68 NA −0.398830868 7.05E−21 Trib1 NA 0.331693479 7.49E−21 Akr1c19 NA −0.272667086 7.78E−21 Cpne3 NA 0.258007443 8.12E−21 Pnpla7 2.65E−15 −0.301626901 1.01E−20 Dnajb11 NA 0.315357308 1.04E−20 Phc2 NA 0.31203626 1.14E−20 Atp6v1f NA −0.252893521 1.18E−20 Tars NA 0.492059498 1.28E−20 Ctnnb1 NA 0.295681078 1.58E−20 Id3 NA −0.351088732 1.84E−20 Tmem243 NA −0.379053275 2.35E−20 Eci1 NA −0.276383144 2.48E−20 Lap3 NA −0.364371999 2.65E−20 Cebpa NA −0.39155301 3.89E−20 Tfpi2 NA −0.366342462 4.58E−20 Il6ra NA 0.304392668 5.08E−20 Cald1 NA 0.373703655 5.69E−20 Neat1 NA 0.63740381 5.72E−20 Ptprf NA 0.307126385 6.50E−20 Uqcrb NA −0.408416744 6.59E−20 Ostc NA 0.265829876 7.22E−20 Sec31a NA 0.263042758 7.68E−20 Mbnl1 NA 0.451258107 9.50E−20 Osbpl9 NA 0.278773264 1.04E−19 Alad NA −0.420641438 1.16E−19 Gch1 NA −0.282499843 1.62E−19 Lrrfip2 NA 0.373099277 1.85E−19 Ireb2 NA 0.265741209 1.87E−19 Cisd1 NA −0.372694857 2.37E−19 Mocs2 NA −0.346681141 2.62E−19 Coa6 NA −0.411409685 2.73E−19 Mrc1 NA 0.340444916 2.90E−19 Copb2 NA 0.283928956 3.01E−19 Stk17b NA 0.291050054 3.56E−19 Ghr NA −0.364775879 3.66E−19 Ptp4a1 NA 0.262691158 3.82E−19 Osbpl1a NA 0.272788799 4.18E−19 Atp5g3 NA −0.300221819 4.43E−19 Cyp27a1 NA −0.373510332 4.44E−19 Akr1a1 NA −0.326935362 4.63E−19 Atp5c1 NA −0.347648538 5.04E−19 Nme1 4.26E−14 −0.432885306 5.43E−19 Azin1 NA 0.270139699 6.16E−19 Purb NA 0.35248294 6.99E−19 Timm8b NA −0.393581904 8.39E−19 Uhrf1bp1l NA 0.419802385 8.66E−19 Sfpq NA 0.393977901 9.08E−19 Gsk3b NA 0.406458835 9.12E−19 Iqgap2 NA 0.254698841 9.72E−19 Cideb NA −0.368365389 1.02E−18 Ndufc2 NA −0.425284817 1.02E−18 Palld NA 0.341357023 1.34E−18 D10Jhu81e NA −0.395730917 1.93E−18 Pxmp2 NA −0.367129885 2.40E−18 15-Sep NA −0.409167133 2.53E−18 Smg1 NA 0.334990596 2.85E−18 Aass NA 0.477517138 3.07E−18 Hnrnpdl NA 0.397994117 3.09E−18 Akap11 NA 0.346362286 4.54E−18 Nedd4l NA 0.281232817 4.90E−18 Jhdm1d NA 0.304101624 4.92E−18 1500011K16Rik NA −0.329639846 5.16E−18 Rps3 NA −0.349320751 5.25E−18 Slc22a30 1.34E−16 −0.374598404 5.26E−18 Erp44 NA 0.279450299 5.51E−18 Coro1c NA 0.306679199 6.74E−18 Ptpn2 NA 0.273418437 7.37E−18 Commd6 NA −0.364529559 7.88E−18 Fitm1 NA −0.324153911 7.90E−18 Dgat2 NA −0.343266251 8.35E−18 Surf4 NA 0.258577589 9.74E−18 Gm10801 NA 0.265934225 1.30E−17 Cox6b1 NA −0.362017449 1.47E−17 Adtrp NA −0.366413277 1.53E−17 Ankrd11 NA 0.415626852 1.70E−17 Ccbl1 NA −0.36488302 2.18E−17 Ftl1 1 1 2.43E−17 Prkaa2 NA 0.263640766 2.46E−17 Arl6ip1 NA −0.364945533 2.55E−17 Egr1 NA 0.584558888 2.80E−17 Dnajb9 NA 0.25864192 2.89E−17 Smdt1 NA −0.367317155 3.21E−17 Ddc NA −0.360752783 3.48E−17 Ndufc1 NA −0.344432714 3.78E−17 Ndufb8 NA −0.348076577 3.81E−17 Zbtb20 NA 0.471532978 4.06E−17 Xiap NA 0.26016306 4.75E−17 Tjp1 NA 0.286163863 4.89E−17 Anp32a NA −0.316957742 5.23E−17 Ide NA 0.251691529 5.60E−17 Ehhadh NA −0.250472633 7.29E−17 Sptbn1 NA 0.42268289 7.32E−17 Mbl2 NA −0.346518253 7.59E−17 Kpnb1 NA 0.280415627 7.91E−17 Mien1 NA −0.370437762 8.08E−17 Gne NA −0.425142761 9.04E−17 Bola3 NA −0.368862428 1.08E−16 Akap13 NA 0.495253767 1.14E−16 Hist1h1c NA −0.300906532 1.17E−16 Nr2f6 NA −0.375433952 1.37E−16 Ces1f NA −0.312589958 1.45E−16 Ndufv3 NA −0.397145193 1.45E−16 Cast NA 0.400886525 1.50E−16 Golga4 NA 0.352084678 1.56E−16 Apom NA −0.302410414 1.68E−16 Ebp NA −0.355328266 1.79E−16 Gpam NA 0.250377871 1.86E−16 Edf1 NA −0.381679393 1.87E−16 Srebf1 NA 0.27619787 1.90E−16 Ndufs8 NA −0.361439192 1.93E−16 Eprs NA 0.37008595 1.94E−16 Ndufa1 NA −0.364515751 1.96E−16 Litaf NA 0.394366845 2.04E−16 H6pd NA 0.343718187 2.22E−16 Bptf NA 0.324463857 2.66E−16 Ifrd1 NA 0.490389826 2.92E−16 Plk3 NA 0.416624571 3.12E−16 Nadk2 NA 0.257852312 3.23E−16 Myl12a NA 0.390780681 3.32E−16 Psmb1 NA −0.358482353 3.95E−16 Baat NA −0.308582001 4.31E−16 Cnpy2 NA −0.372850093 4.94E−16 Bhmt2 NA −0.311413339 5.24E−16 Gstm4 NA −0.380861133 5.61E−16 Chac2 NA −0.286511682 6.00E−16 Mettl20 NA −0.331367185 6.50E−16 Bckdha NA −0.349979609 6.82E−16 BC089597 NA 0.262237515 6.90E−16 Sirt3 NA −0.345997558 7.30E−16 Mdm2 NA 0.328296258 8.15E−16 Acy3 NA −0.313748988 8.20E−16 Hsp90ab1 NA 0.322748941 8.34E−16 Mrpl12 NA −0.308200176 9.04E−16 Fam120a NA 0.280043634 9.81E−16 Atp5o NA −0.331628292 9.93E−16 Fkbp4 NA −0.353366286 1.01E−15 Cldn3 NA −0.314469359 1.08E−15 Ipo5 NA 0.268735631 1.12E−15 Fpgs NA −0.34940945 1.15E−15 Sdsl NA 0.259290764 1.41E−15 Tgm2 NA 0.399330712 1.43E−15 Phlda1 NA 0.549174347 1.46E−15 Macf1 NA 0.404177263 1.47E−15 Mrps18c NA −0.366291099 1.60E−15 Sbno1 NA 0.367100512 1.62E−15 Nedd8 NA −0.356380686 1.86E−15 Magt1 NA 0.263295188 1.95E−15 Sdhb NA −0.289642823 2.09E−15 Ethe1 NA −0.333417645 2.45E−15 Mdh1 NA −0.307657821 3.99E−15 Nrip1 NA 0.272854584 4.11E−15 Lcp1 NA 0.484011001 4.22E−15 Srsf11 NA 0.401209055 4.47E−15 Shb NA 0.315236194 4.68E−15 Bsg NA −0.31515012 5.31E−15 Hibch NA −0.327130099 6.26E−15 Mki67ip NA 0.318372964 6.27E−15 Otc NA −0.29903416 6.99E−15 Smap2 NA 0.348911433 9.52E−15 Nr0b2 NA −0.293010319 1.07E−14 Pank1 NA −0.352650118 1.09E−14 Ak2 NA −0.345102135 1.13E−14 Rlim NA 0.31023282 1.42E−14 Erbb2ip NA 0.333163506 1.69E−14 Huwe1 NA 0.387931325 1.75E−14 Hmgcs1 NA −0.349112403 1.98E−14 Rps21 NA −0.364450868 2.02E−14 Grhpr NA −0.353058662 2.13E−14 Tm7sf2 NA −0.316381125 2.28E−14 Txn1 NA −0.309123787 2.50E−14 Sh3bgrl NA 0.25128227 2.71E−14 0610011F06Rik NA −0.303688511 2.80E−14 Psmb6 NA −0.319377533 2.87E−14 Gm2788 NA −0.283138796 2.89E−14 AW112010 NA −0.298104828 3.17E−14 Dhdh NA −0.334814135 4.04E−14 Sf1 NA 0.30230624 4.12E−14 Tbl1xr1 NA 0.307509115 4.15E−14 Coq9 NA −0.347936449 4.20E−14 Il4ra NA 0.25739098 4.44E−14 Tceb2 NA −0.32073626 4.50E−14 Rps10 NA −0.33690905 4.59E−14 Psme4 NA 0.262584214 4.62E−14 Gm4951 NA −0.322087312 5.37E−14 Pak2 NA 0.281467155 5.57E−14 Metap2 NA 0.368604828 6.59E−14 2010107E04Rik NA −0.318247806 7.21E−14 Prox1 NA 0.266329524 7.66E−14 Ddx6 NA 0.444275069 7.70E−14 Pacsin2 NA 0.370825053 7.89E−14 Hdac11 NA −0.33684651 8.63E−14 Ubl5 NA −0.303313218 1.12E−13 Mettl7a1 NA −0.322098553 1.21E−13 Larp4b NA 0.34214672 1.22E−13 Uqcc2 NA −0.326858302 1.27E−13 1810022K09Rik NA −0.300081452 1.29E−13 Selk 1.30E−13 −0.338314398 1.30E−13 Dhx9 NA 0.350364065 1.41E−13 Psmb3 NA −0.330302519 1.47E−13 Rexo2 NA −0.3263129 1.48E−13 Hipk3 NA 0.339385214 1.58E−13 Cyp4f14 NA −0.295933211 1.60E−13 Wdr26 NA 0.432510772 1.94E−13 Sec61b NA −0.290284119 2.20E−13 Paqr9 NA −0.332341635 2.23E−13 Tsc22d1 NA −0.299728636 2.38E−13 Glyctk NA −0.297701904 2.68E−13 Mapk6 NA 0.256831906 3.22E−13 Atp1b1 NA 0.370203015 3.27E−13 Aqp9 NA −0.310863805 3.38E−13 Suco NA 0.250962583 3.39E−13 Dync1h1 NA 0.379607116 4.50E−13 Ctsb NA 0.521310448 4.83E−13 Tpr NA 0.440921219 5.22E−13 Supt6 NA 0.291294768 5.48E−13 Lsmd1 NA −0.313140806 5.95E−13 Kif21a NA 0.404170578 6.46E−13 Sgk1 NA 0.284303028 7.18E−13 Proz NA 0.263204472 7.77E−13 Romo1 NA −0.335854841 7.99E−13 Cfhr1 NA −0.325332852 8.01E−13 Deptor NA 0.260618372 8.58E−13 Atp2b1 NA 0.332096305 9.01E−13 Rnf13 NA 0.255296715 9.16E−13 Dhrs4 NA −0.332074421 9.59E−13 Lasp1 NA 0.253021439 9.93E−13 Tmem147 NA −0.283785217 1.00E−12 Fus NA 0.339324351 1.03E−12 Yap1 NA 0.328109852 1.07E−12 Acads NA −0.32421998 1.10E−12 Fam25c NA −0.297673676 1.12E−12 Ndufb3 NA −0.327185415 1.16E−12 Agpat2 NA −0.298159013 1.22E−12 Bst2 NA −0.315565973 1.52E−12 Caprin1 NA 0.262825966 1.56E−12 Syncrip NA 0.27476476 1.65E−12 Rnaseh2c NA −0.325683719 1.67E−12 Cldn2 NA −0.251076838 1.86E−12 Klf3 NA 0.267357487 1.89E−12 Tnks2 NA 0.317626402 1.91E−12 Derl2 NA −0.331734152 2.28E−12 Ndufv2 NA −0.327639406 2.48E−12 Eif4b NA 0.36816236 2.53E−12 Cyp4f15 NA −0.299840345 2.53E−12 Brd2 NA 0.571515166 2.65E−12 Copz1 NA 0.257722711 2.65E−12 Ddx27 NA 0.252155421 3.46E−12 Mcee NA −0.31991829 3.52E−12 Dnajc19 NA −0.316006732 3.54E−12 Aldh4a1 NA −0.29070878 3.75E−12 Fdps NA −0.266347718 4.58E−12 Reep3 NA 0.409014614 5.12E−12 Car5a NA −0.308769058 5.42E−12 Tmem37 NA −0.282207793 6.77E−12 Tspo NA −0.315729205 6.95E−12 Tspan31 NA −0.295881364 7.18E−12 Atp11c NA 0.260536506 7.22E−12 Atf6 NA 0.377819844 7.66E−12 Rpl14 NA −0.277637754 7.87E−12 Med13 NA 0.294918978 7.95E−12 Sdr9c7 NA −0.259988635 8.11E−12 Rps8 8.37E−12 −0.274601282 8.37E−12 Kpna1 NA 0.32304803 8.67E−12 Btaf1 NA 0.275463861 8.92E−12 Ddah1 NA −0.312000429 9.85E−12 Ndufs4 NA −0.313160933 1.01E−11 Fam214a NA −0.265769677 1.02E−11 Rbm25 NA 0.421459678 1.03E−11 Ndufb10 NA −0.300358086 1.04E−11 Slirp NA −0.308519262 1.04E−11 Scaf11 NA 0.359845436 1.30E−11 Anapc13 NA −0.364181956 1.31E−11 Arpc1b NA 0.259676842 1.36E−11 Pnkd NA −0.292772175 1.41E−11 Abcd3 NA −0.271805105 1.44E−11 Hmgcr NA 0.416711628 1.61E−11 Mxd1 NA 0.297767874 1.65E−11 Bet1 NA −0.296563627 1.73E−11 Cela1 NA −0.272296838 1.78E−11 Tmem160 NA −0.339044834 2.24E−11 Snx10 NA 0.285642594 2.35E−11 Ubb       0.120646029 −0.275030382 2.58E−11 Lgals9 NA −0.269998113 2.87E−11 Aadat NA −0.318627951 3.04E−11 Mrpl33 NA −0.265447876 3.06E−11 Tmem258 NA −0.27689533 3.18E−11 Cyp2d40 NA −0.321717407 3.46E−11 Birc6 NA 0.344367807 3.56E−11 Naprt1 NA −0.338143058 4.15E−11 Agxt NA −0.258383387 4.28E−11 Kdelr2 NA 0.397729248 4.46E−11 Stbd1 NA −0.273216024 5.39E−11 Phf20l1 NA 0.308488005 5.49E−11 Tmprss6 NA −0.280234101 5.62E−11 Gstk1 NA −0.282802747 5.77E−11 Gadd45gip1 NA −0.304090556 6.25E−11 Ubr4 NA 0.330144527 7.63E−11 Sigmar1 NA −0.305468332 7.64E−11 Ythdc1 NA 0.264130576 8.40E−11 Psma6 NA −0.30353658 8.48E−11 Acaa1a NA −0.301848759 9.21E−11 Cyp2c55 NA −0.290435372 9.36E−11 Proc NA −0.270719362 9.66E−11 Mrpl20 NA −0.309348635 1.03E−10 Myeov2 NA −0.305189789 1.05E−10 Dnajc5 NA 0.326483514 1.16E−10 Kdm5a NA 0.351390096 1.27E−10 Commd3 NA −0.265556375 1.46E−10 Mrpl42 NA −0.284507519 1.47E−10 Bdhl NA −0.293611347 1.50E−10 Mrpl15 NA −0.291228504 1.56E−10 Abcb11 NA −0.261778471 1.57E−10 Ddost NA 0.250356033 1.89E−10 Anxa5 NA 0.365372347 2.08E−10 Gsr NA 0.412829579 2.10E−10 Atf4 NA 0.341134734 2.33E−10 Iah1 NA −0.292985785 2.41E−10 Pdzd8 NA 0.286270568 2.46E−10 Fbxo21 NA −0.263087536 2.85E−10 Ftsj3 NA 0.255227431 2.86E−10 C6 3.03E−10 −0.26698766 3.03E−10 Acot13 NA −0.288638646 3.05E−10 Acat3 NA −0.311510623 3.16E−10 Magi3 NA 0.269961841 3.24E−10 Cybb NA 0.377799564 3.48E−10 Tmem242 NA −0.272538433 3.57E−10 Mrpl41 NA −0.267412137 3.73E−10 Sema4g NA −0.250459516 3.89E−10 Cap1 NA 0.325055169 4.46E−10 Csrp3 NA −0.293996249 4.47E−10 Hpn NA −0.268601326 4.81E−10 Slc25a51 NA 0.263985158 6.14E−10 Spcs1 NA −0.26287037 6.30E−10 Apof NA −0.252173807 6.73E−10 Cep85 NA 0.28389234 6.87E−10 Aes NA −0.264214993 7.53E−10 Pet100 NA −0.28003555 7.60E−10 Gcat NA −0.258728349 7.71E−10 Rps24 NA −0.262473665 8.21E−10 Dcaf11 NA −0.281659388 9.55E−10 Pmpcb NA −0.263615722 1.03E−09 Lipc NA −0.254841484 1.09E−09 Ptpn11 NA 0.277804552 1.15E−09 Ccdc50 NA 0.285830087 1.18E−09 Ivns1abp NA 0.356610399 1.20E−09 Nqo2 NA −0.267802053 1.22E−09 Abcg2 NA −0.280923445 1.38E−09 Dera NA −0.267441985 1.43E−09 Fasn NA 0.291406736 1.44E−09 Rabac1 NA −0.265987205 1.45E−09 Gm20594 1.55E−09 −0.360000649 1.55E−09 Clic4 NA 0.299795775 1.64E−09 Ugt3a2 NA −0.258613351 1.89E−09 Mvd NA −0.270409867 1.91E−09 Ptpmt1 NA −0.255981462 2.02E−09 0610007P14Rik NA −0.257015045 2.31E−09 Swi5 NA −0.262086804 2.33E−09 Tpi1 NA −0.26157943 2.35E−09 Plcxd2 NA −0.275192522 2.48E−09 Tmem150a NA −0.253507791 2.61E−09 Rnf169 NA 0.333974467 2.63E−09 Deb1 NA −0.267029156 2.74E−09 Hsbp1 NA −0.286726926 2.99E−09 Slc26a1 NA −0.28165635 3.01E−09 Rsl1d1 NA 0.346056141 3.82E−09 Map3k2 NA 0.251791147 3.83E−09 Abcf1 NA 0.303190272 4.09E−09 Psma1 NA −0.256671259 4.64E−09 Fam195a NA −0.264890901 4.66E−09 Mrpl11 NA −0.268482417 4.92E−09 Selo NA −0.257421903 5.24E−09 Plbd2 NA 0.264873115 5.33E−09 Rap1b NA 0.340766029 6.89E−09 Ppip5k2 NA 0.320939415 7.41E−09 Pcm1 NA 0.265397644 8.07E−09 Acsm5 NA −0.261394035 8.53E−09 Rangap1 NA 0.296226768 1.08E−08 Rraga NA 0.262613483 1.10E−08 1110058L19Rik NA −0.258088587 1.12E−08 Dsp NA 0.265533344 1.15E−08 Ccnl1 NA 0.256623048 1.44E−08 Chmp4b NA 0.300153098 1.52E−08 Ubr5 NA 0.305718363 1.72E−08 Net1 NA 0.34785505 1.84E−08 H2-D1 NA 0.286522764 2.31E−08 Srd5a1 NA −0.277347272 2.35E−08 Papss2 NA −0.254475327 2.73E−08 Dnaja2 NA 0.372342331 2.79E−08 Srrm2 NA 0.328159189 3.12E−08 Herc1 NA 0.256188826 3.26E−08 Gtf2a2 NA 0.279207862 3.58E−08 Pkp4 NA 0.323033636 4.02E−08 Trip11 NA 0.347886673 4.15E−08 Slc16a2 NA −0.251969763 4.57E−08 Ctsc NA 0.361021766 4.80E−08 Megf9 NA 0.276890033 6.26E−08 Mrpl28 NA −0.269896048 6.87E−08 Rpl34 NA −0.297598539 8.13E−08 Mrpl34 NA −0.283750306 8.42E−08 Mgea5 NA 0.32630901 9.07E−08 C1d NA −0.255261652 9.45E−08 Gcgr NA −0.257636913 1.04E−07 Sptan1 NA 0.312663889 1.10E−07 Zfp259 NA 0.255636639 1.10E−07 Xrn2 NA 0.298471923 1.28E−07 Hipk1 NA 0.291600227 1.40E−07 Alcam NA 0.323788815 1.46E−07 Gnas NA 0.258853087 1.47E−07 Mapkapk2 NA 0.31382654 1.63E−07 Coasy NA −0.253428655 1.78E−07 Gars NA 0.257638792 2.09E−07 Diap1 NA 0.325941798 2.10E−07 Rab6a NA 0.32343226 2.23E−07 Pvrl2 NA −0.261260991 2.66E−07 2810428115Rik NA −0.263117928 2.80E−07 Nucks1 NA 0.355785584 2.82E−07 Hnrnpu NA 0.339415607 3.35E−07 Chuk NA 0.372437977 5.21E−07 Serbp1 NA 0.322652522 5.43E−07 Ctnnd1 NA 0.251848095 5.48E−07 Nploc4 NA 0.291804954 5.69E−07 Zfp106 NA 0.336920255 6.34E−07 Arhgdia NA 0.256326455 7.14E−07 BC005537 NA 0.354337911 1.05E−06 Akr1e1 NA −0.258207619 1.09E−06 Eific NA 0.301979757 1.10E−06 Tmem86b NA −0.258236533 1.18E−06 Mrps12 NA −0.250441318 1.26E−06 Cdh1 NA 0.269696738 1.61E−06 Ddx3y NA 0.339517654 1.83E−06 Ndufa5 NA −0.251988986 1.96E−06 Ppm1g NA 0.252225215 2.04E−06 Elovl5 NA 0.335236661 2.54E−06 Impad1 NA 0.32267465 3.04E−06 Tab2 NA 0.348412001 3.51E−06 Cyp3a13 NA 0.284411943 4.93E−06 Pgls NA −0.274714156 5.62E−06 Actr3 NA 0.275997927 5.66E−06 St3gal4 NA 0.275033534 5.81E−06 4932438A13Rik NA 0.287850722 7.97E−06 Abce1 NA 0.279955892 8.43E−06 Pde3b NA −0.258970093 8.55E−06 Smoc1 NA 0.26157412 8.57E−06 4931406C07Rik NA −0.254363633 9.62E−06 Rmnd5a NA 0.318903459 1.09E−05 Ash11 NA 0.265693821 1.23E−05 Sf3b1 NA 0.28884767 1.32E−05 Spag9 NA 0.318820155 1.33E−05 Nek7 NA 0.291098417 1.63E−05 Eif4a1 NA 0.251906299 2.25E−05 Usp7 NA 0.287320099 2.90E−05 Tbca NA −0.27261031 3.43E−05 Pi4k2a NA 0.353561144 3.46E−05 Prpf19 NA 0.25876049 3.47E−05 Usp34 NA 0.285942387 5.16E−05 Slc16a10 NA −0.254826191 9.62E−05 Eea1 NA 0.261201113 0.000132332 Sars NA 0.276853119 0.00019395 Herc4 NA 0.267474882 0.000255647 Gadd45a NA 0.282867411 0.000337547 Bc1af1 NA 0.26848767 0.000425718 Gm5424 NA 0.269800095 0.000520866 Slc35d1 NA 0.309435259 0.000579989 Cu11 NA 0.259206487 0.000597201 Cu13 NA 0.278802183 0.000803381 Slc30a1 NA 0.250570123 0.000818871 Eifia NA 0.314713983 0.00096785 Tln1 NA 0.321033046 0.001767724 Zfand5 NA 0.28815165 0.00189648 Glul      0.00256055 0.379494728 0.00256055 Eif4ebp1 NA 0.261682735 0.003063164 Hectd1 NA 0.30802968 0.003395612 Gldc NA 0.280156601 0.00370491 Rassf3 NA 0.291236708 0.004723315 Nudt4 NA 0.25418892 0.007016738 Rock1 NA 0.2607635 0.009308994 Rbm39 NA 0.265732671 0.012545192 Abcc2 NA 0.289681267 0.018266512 Naa50 NA 0.265659058 0.019114384 Pa2g4 NA 0.289349263 0.02381992 Riok3 NA 0.291562038 0.055677881 Myo1b NA 0.262427327 0.075213075 Eifib NA 0.250328103 0.08550598 Ldlr NA 0.282025946 0.146582345 Psap NA 0.360973931 0.257800256 Gda NA 0.627476336 0.266276129 Gnai2 NA 1 0.281667665

TABLE 8B Differentially expressed genes between treatment (PH and UT). ID PH3logFC PH48logFC PH120logFC PH3p PH48p Saa2 2.971862499 4.43818759 3.598008691 0 0 Mt1 2.610854994  1.733946488 1.65972779  0  9.88E−293 Mt2 2.6060431   1.558205591 1.471840722 0  2.04E−271 Saa1 2.202156726  3.650785996 2.959370227 0 0 Steap4 1.890015167  0.631013696 0.931387724 0 4.71E−63 Serpina3n 1.759758939  1.082720183 1.205364333 0  4.67E−169 Lcn2 1.499141183 2.39758181 2.127649068 0 0 Lpin1 1.327657625 NA 0.382955017 0 NA n-R5-8s1 1.289598504  1.223121237 1.066654791 0  2.94E−283 Igfbp1 1.288789902  0.466237818 0.488899754 0 2.67E−25 Cxcl1 1.230398019  0.353012683 NA 0 7.28E−05 Scd1 1.081676999 NA 0.787835318 0 NA Gm26924 1.063463323  1.445355764 1.379756734 0 0 Il1r1 0.998168131  0.299449962 0.63980318  0 2.79E−18 Fga 0.981249724  0.968748472 1.039432587 0  9.27E−246 Gm24601 0.924568273  0.675379727 0.675086715 0  2.68E−176 Nnmt 0.901052904  0.768076272 0.508818069 0  3.84E−107 Itih4 0.887186241  1.171742648 1.18011817  0 0 St3gal5 0.882761517 NA NA 0 NA Tacc2 0.877623973 NA NA 0 NA Lrg1 0.870250525  1.051046086 1.260509735 0  1.54E−213 Fam134b 0.865578177 NA NA 0 NA Tat 0.857965136  0.369618242 0.614979826 0 2.45E−45 Saa4 0.854921603  0.635837715 1.158596154 0 6.90E−79 Thrsp 0.836598219 −0.374383397 −0.629247506  0 1.55E−18 Slc39a14 0.831584936 NA 0.506662289 0 NA Lars2 0.816795688  0.849538102 1.419129056 0  4.73E−222 Fgg 0.809322713  0.702140119 0.686743278 0  3.42E−167 Slc38a2 0.797899442 NA 0.333158401 0 NA Serpina3m 0.779052745  0.519751144 0.305171041 0 1.28E−57 Hp 0.774785279  1.584889895 1.107075607 0 0 Fgb 0.739519125  0.677592366 0.605783409 0  1.41E−179 Gm15564 0.735157137  0.746211054 1.485885928 0  4.32E−146 Serpina10 0.733655099  0.871044179 0.740578005 0  3.60E−107 Plin2 0.720463076 NA NA 0 NA Fmo5 0.690160801  0.379271143 0.337493236 0 1.75E−43 Fkbp5 0.663304836 NA NA 0 NA Slc25a47 0.635928777 −0.555532536 NA 0  2.81E−104 Mat1a 0.623734998  0.378728792 0.519634823 0 5.65E−41 Acox1 0.540022158 NA 0.292890336 0 NA Aldob 0.490200848 −0.254127817 NA 0 2.25E−64 C3 0.482674202  0.982337034 1.071950932 0 0 B3galt1 0.788734938 NA 0.251993915 3.52E−301 NA Fn1 0.684266092  0.469732274 1.018772906 5.56E−298 5.12E−32 Hnf4a 0.644195253 NA 0.470873585 5.68E−290 NA Btg2 0.772686832  0.280923811 0.386164963 7.24E−290 2.37E−05 H3f3b 0.755567107 NA NA 4.44E−288 NA Aass 0.705615345 NA 0.312355615 1.07E−286 NA Sephs2 0.618707003 NA 0.604852301 1.06E−281 NA Cldn14 0.511583526 NA NA 4.32E−281 NA Rcan1 0.509239866 NA NA 4.58E−279 NA Hspb8 0.667847253 NA 0.52383406  9.19E−267 NA Arhgef26 0.568544702 NA 0.276634335 4.92E−265 NA Slc7a2 0.622326529 NA 0.374380964 6.74E−265 NA Pfkfb3 0.426580733 NA NA 3.82E−264 NA Pck1 0.43447474  NA 0.495042924 4.86E−264 NA Errfi1 0.500850526 NA NA 7.43E−262 NA Gjb2 0.639507436  0.328679811 0.402811227 9.92E−255 2.44E−12 Snx10 0.558244633  0.253822304 NA 1.59E−251 1.28E−13 Bcl3 0.419650143 NA NA 3.05E−251 NA Hpx 0.460272423  1.443685235 0.994363825 2.87E−247 0 Bach1 0.533237374 NA NA 5.54E−247 NA Tifa 0.392339477 NA 0.321485305 3.72E−241 NA 2010003K11Rik 0.372219971 NA NA 1.06E−239 NA Pzp 0.387351113  0.382796555 0.636851805 2.85E−237 2.61E−52 Tiparp 0.489122153 NA NA 7.07E−236 NA Rapgef4 0.588317735 NA NA 4.64E−233 NA Mup10 0.428268029  0.281431551 0.254194035 1.14E−231 4.82E−45 Egfr 0.555834247 NA 0.65440823  5.47E−228 NA mmu-mir-6236 0.468866739  0.632369146 1.257248389 4.51E−221 5.49E−97 Etnk2 0.592353201 NA NA 7.87E−221 NA Mfsd2a 0.496351884 NA NA 1.64E−219 NA Txnip 0.552612237 −0.310098222 NA 1.04E−218 1.24E−19 Arg1 0.381616351 NA NA 2.23E−218 NA Gpt2 0.533331785 NA NA 3.67E−218 NA Slc25a25 0.544465891 NA 0.442662636 2.55E−217 NA Actb 0.456981443  0.399035393 NA 2.15E−210 2.62E−44 Xbp1 0.539986   NA NA 1.34E−208 NA Upp2 0.541753512 −0.265836776 NA 2.02E−206 1.03E−24 Fbf1 0.298573909 NA NA 4.53E−206 NA Plin5 0.489257529 NA NA 1.01E−205 NA Plk3 0.488016367 NA NA 8.22E−205 NA Trib1 0.581754281 NA NA 1.57E−204 NA Mtss1 0.552137981 NA 0.339863924 2.07E−204 NA Klf6 0.3616937  NA NA 8.00E−203 NA Itih3 0.469631651  1.223022315 1.177912468 1.12E−197  4.04E−297 Slc10a2 0.30563824  NA NA 6.54E−197 NA Sdc4 0.43560504  NA 0.315436107 2.70E−193 NA Atf3 0.597274889 NA 0.262281273 1.23E−191 NA Ptp4a1 0.393137367 NA NA 6.10E−190 NA Prg4 0.480504574  0.3555459X5 0.810835665 4.35E−189 1.45E−24 Rgs16 0.438105488 NA NA 3.55E−188 NA Gpcpd1 0.53780646  NA NA 5.36E−188 NA Rhob 0.37207281  NA NA 4.39E−187 NA Glul 0.478908893  0.611936929 0.495360357 1.01E−186 1 Fam35a 0.470461753 NA NA 7.67E−186 NA Klf10 0.304779554 NA NA 1.06E−185 NA Egr1 0.620480469 NA 0.271667356 7.27E−185 NA Apcs 0.573439593  2.049485412 0.965147497 2.06E−182 0 Shb 0.430613558 NA NA 4.03E−182 NA Orm1 0.463411533  1.823760769 1.05827481  4.58E−180 0 Fgl1 0.49338252   1.561880768 1.379926505 2.36E−175 0 1810055G02Rik 0.382584093 NA NA 7.73E−175 NA Stat3 0.460515229  0.308012615 0.483904634 3.58E−174 2.82E−05 Abca1 0.50506234  NA 0.370856836 3.19E−172 NA Igfbp4 0.387861679 NA 0.411174683 6.69E−171 NA Got1 0.542891511 NA 0.331700716 7.82E−171 NA Cdkn1a 0.449325471 NA NA 7.06E−169 NA Apob 0.416824707 NA 0.505397578 8.05E−169 NA Gfra1 0.474694426 NA NA 4.73E−168 NA Ivns1abp 0.46254094  NA NA 9.44E−168 NA Slc41a2 0.3685439   0.318516467 0.441321771 2.22E−166 5.60E−25 Slc25a51 0.372157664 NA NA 1.11E−164 NA Myo1e 0.399456672 NA NA 7.83E−162 NA Gm23935 0.498066925  0.562414557 1.207244314 8.57E−162 2.21E−73 Bhlhe40 0.403249298 NA 0.370112004 3.04E−158 NA Ddx3x 0.47100162  NA NA 1.36E−155 NA Tmem87b 0.288330587 NA NA 8.72E−155 NA Dak 0.481947664 NA NA 1.71E−153 NA Slc25a22 0.390931532 NA NA 7.19E−153 NA Fasn 0.467168076 NA NA 2.55E−152 NA Fh1 0.471428771 NA NA 7.97E−152 NA Rnf103 0.438540394 NA NA 1.39E−149 NA Sds 0.787094904 −0.352238286 NA 5.50E−149 7.99E−43 B4galt1 0.321380868 NA NA 4.77E−146 NA Cps1 0.336429448 NA 0.312297912 1.19E−145 NA Atp1b1 0.424801231 NA NA 1.32E−145 NA Jmjd1c 0.39612601  NA NA 1.05E−144 NA Gm26917 0.46739621   0.475554164 0.443747552 2.42E−144 2.52E−05 Junb 0.458500682 NA NA 1.57E−143 NA 4933426M11Rik 0.28624304  NA NA 1.78E−142 NA Pik3r1 0.389193614 NA NA 1.89E−142 NA D10Wsu102e 0.256022156 NA NA 1.03E−141 NA Hyou1 0.431109873  0.315760783 0.496156079 3.60E−141 0.000165574 Glud1 0.341724783  0.359099708 0.307823999 1.11E−139 4.69E−47 Cpt1a 0.42860734  NA 0.276570679 3.31E−139 NA Epas1 0.38425941  NA NA 2.12E−138 NA Jun 0.479246114 NA NA 2.64E−135 NA Mbd1 0.348094524 NA NA 2.44E−134 NA Rnd3 0.285147682 NA NA 4.66E−134 NA Litaf 0.396007707 NA NA 2.34E−132 NA Ptpn1 0.268263225 NA NA 6.92E−130 NA Bcl2l1 0.280315334 NA NA 1.17E−128 NA Grn 0.403315761  0.293077345 0.316049742 3.44E−128 4.47E−10 Tns1 0.33981795  NA NA 4.58E−128 NA Slc25a15 0.402049896 NA 0.393990477 6.99E−128 NA Gadd45g 0.392031882 −0.336240737 NA 7.78E−128 3.29E−30 Wbp1l 0.409138156 NA NA 1.29E−127 NA Foxa3 0.307992015 NA NA 2.28E−126 NA Myh9 0.399128031  0.438269269 0.631035657 3.04E−126 1.59E−15 Fos 0.524733327 NA NA 3.55E−125 NA Id2 0.430147785 −0.333366521 NA 5.03E−124 1.37E−46 Itih2 0.336714211  0.312933325 NA 1.56E−122 2.29E−24 Plg 0.26619661  NA 0.596524395 1.35E−121 NA Qsox1 0.378486857  0.551776463 0.725062115 3.75E−121 2.24E−55 Ccnl1 0.341338448 NA NA 1.67E−120 NA Eef1a1 0.340768186  0.254969818 NA 6.14E−119 1.25E−12 Ier2 0.452598264 NA NA 1.60E−118 NA Elovl6 0.37962641  NA NA 5.92E−117 NA Nedd4l 0.271827098 NA NA 1.51E−116 NA Ppip5k2 0.30299148  NA NA 3.63E−115 NA Epb4.1 0.349430673 NA NA 1.93E−113 NA Cfh 0.312615767  0.588715272 0.83288399  3.46E−113  2.52E−103 Ulk1 0.297841785 NA NA 5.13E−113 NA Ell2 0.371745977 NA NA 9.30E−113 NA Tnfrsf1a 0.346845029 NA 0.267537895 3.42E−112 NA Eif4g2 0.384302798 NA 0.287105046 2.51E−110 NA Ly6e 0.42022985   0.525599776 1.093957206 1.47E−108 5.02E−20 Il6ra 0.251696836 NA NA 2.93E−108 NA Lpgat1 0.390146943  0.347767347 0.400787984 1.25E−107 1.05E−09 Fads2 0.323744791 NA NA 4.78E−106 NA Atl2 0.321873809 NA NA 5.02E−106 NA Dst 0.329905553 NA NA 7.40E−105 NA Jak1 0.362766687 NA NA 2.44E−103 NA Nfil3 0.338730712 NA NA 5.23E−103 NA Elovl5 0.382267188 NA NA 1.08E−102 NA Mgll 0.321840174 NA NA 6.61E−101 NA Sult1a1 0.371023537  0.344836675 NA 2.67E−99  2.16E−12 Man2a1 0.369999358 NA 0.323273082 3.60E−98  NA Eef2 0.289562847 NA 0.321705764 1.70E−97  NA Aff4 0.344186222 NA NA 7.00E−97  NA Palmd 0.284673594 NA NA 9.43E−97  NA Zfp36 0.407014847 NA NA 1.05E−96  NA Eif1a 0.295219945 NA NA 7.80E−96  NA Slc3a1 0.290117272  0.321802388 0.381791335 1.93E−94  1.78E−11 Ifitm3 0.331673739 NA 0.506857449 3.64E−94  NA Atp2a2 0.350363266 NA 0.263222967 8.21E−94  NA Nop58 0.257566653 NA NA 1.12E−93  NA Enpp2 0.316882991 NA NA 4.48E−93  NA Gm2a 0.341145926 NA NA 6.61E−93  NA Cyb5r3 0.337684684 NA NA 1.90E−92  NA Apoa4 0.609214916  1.186863065 NA 2.34E−92   3.01E−137 Aldh1l1 0.277372649 NA 0.564932962 2.62E−88  NA Eci2 0.288159513 NA NA 5.23E−88  NA Slc38a3 0.292400046 NA 0.353500212 1.28E−87  NA Dusp1 0.300628481 NA NA 1.26E−86  NA Igf1 0.277138761 NA NA 2.86E−86  NA Serinc3 0.293964974 NA NA 2.71E−85  NA Tgm2 0.316575272 0.37123494 0.342526865 5.50E−85  5.94E−16 C8a 0.294064237 NA 0.404198047 1.39E−84  NA Txnrd1 0.314979852  0.252234489 NA 3.22E−84  0.032529357 Asl 0.297673772 NA NA 1.76E−83  NA Por 0.290745567 NA NA 3.93E−83  NA Sec14l4 0.285169227 NA NA 5.54E−83  NA Uroc1 0.329587334 NA 0.459322934 1.13E−82  NA Lrp6 0.270740438 NA NA 1.18E−82  NA Atf6 0.280521162 NA NA 1.55E−82  NA Ddi2 0.302519699 NA NA 2.71E−82  NA Dstn 0.271381717 NA NA 2.90E−82  NA Id3 0.399520373 NA NA 9.94E−82  NA H6pd 0.300492669 NA 0.491965789 1.91E−81  NA Xdh 0.27224472  NA 0.373181784 8.54E−81  NA Tmed5 0.296018777 NA NA 1.36E−80  NA G6pc 0.341403933 −0.259264856 NA 2.15E−80  3.71E−17 Mttp 0.296651415 NA NA 2.14E−79  NA Angptl4 0.315315425 NA NA 2.44E−79  NA Nrp1 0.268796793 NA NA 7.49E−79  NA Fgf1 0.287983029 NA NA 7.97E−79  NA Prox1 0.31520499  NA NA 3.03E−77  NA Gck 0.260705425 NA NA 6.82E−77  NA Picalm 0.276902165 NA NA 1.27E−76  NA Lbp 0.264248666 NA 0.656662588 4.58E−76  NA Azin1 0.268891169 NA NA 7.99E−76  NA Ddx5 0.251675045 NA NA 3.02E−75  NA Cpb2 0.280302458  0.395699062 0.403790403 1.59E−74  1.09E−38 Il6st 0.262348153 NA 0.382881893 3.02E−73  NA Rmnd5a 0.273473023 NA NA 5.48E−73  NA Trp53inp1 0.269278401 NA NA 1.01E−72  NA Ctsb 0.268200419  0.310468937 0.553974491 1.09E−72  2.17E−12 Acsl4 0.250793464  0.273275871 NA 5.43E−70  0.003086449 Elovl2 0.285038606 NA NA 2.60E−69  NA Iqgap2 0.283192936 NA NA 5.91E−69  NA Lrp1 0.310226628  0.314138344 0.914046975 2.25E−68  2.75E−05 Arhgef12 0.280147378 NA 0.304865834 1.49E−67  NA Pim3 0.280137371 −0.255337561 NA 3.27E−67  2.68E−22 C4bp 0.26668764   0.530516995 0.505363658 4.30E−67  7.45E−90 Lrpprc 0.257016288 NA NA 6.41E−67  NA Atp1a1 0.261718912 NA NA 2.96E−65  NA Copa 0.251410027 NA 0.294256247 1.69E−64  NA Acly 0.287663867 NA NA 4.67E−64  NA Rcl1 0.273905375 NA NA 1.37E−63  NA Alas1 0.283195713  0.423999349 0.300367757 6.82E−63  7.65E−32 Kmo 0.262269388 NA 0.305370487 2.45E−62  NA Ppp1r3b 0.259418401 NA NA 1.58E−61  NA Zfp36l1 0.271823824 NA NA 4.54E−61  NA Efna1 0.256152989 NA 0.268455179 2.55E−60  NA Ctsl 0.256520866 NA NA 1.56E−59  NA Ptplad1 0.255273084 NA NA 2.04E−59  NA Hdlbp 0.267317937 NA 0.394030651 3.33E−59  NA Pnpla7 0.251226201 NA NA 4.93E−58  NA Fads1 0.267264464 NA NA 2.35E−57  NA Nedd4 0.259978699 NA NA 7.35E−56  NA Mtus1 0.268076242 NA 0.385483144 2.92E−54  NA Cyp2c70 0.25600888  NA 0.511802822 8.20E−51  NA Brd2 0.258446853 NA NA 8.84E−51  NA Saa3 0.298054041  2.199786317 NA 7.93E−23  0 Orm2 NA  2.405086745 1.536747401 NA 0 Ambp NA 0.4774812  0.496213815 NA  2.69E−163 Trf NA  0.436833817 NA NA  1.60E−148 Rnase4 NA  0.836959148 1.031156304 NA  4.28E−141 Prtn3 NA  0.327267898 0.350182853 NA  8.65E−141 Fam25c NA 0.96762143 NA NA  2.76E−118 Cp NA  0.620221202 0.655511152 NA  1.41E−115 Dhcr24 NA  0.759730578 0.551421264 NA  1.65E−115 Kng1 NA  0.419944891 0.546835494 NA  3.92E−102 Csf2ra NA  0.342712543 NA NA  3.48E−100 D17H6S56E-5 NA  0.560241333 NA NA 2.13E−95 Cxcl14 NA  0.268462966 NA NA 7.87E−89 Hsp90ab1 NA  0.455851506 0.323037124 NA 1.23E−83 Tmem176a NA  0.675060004 0.67082422  NA 3.59E−81 Isyna1 NA  0.320415943 0.270110032 NA 8.49E−80 Cd5l NA  0.460825248 0.49371428  NA 2.07E−79 Ccnd1 NA  0.385849227 NA NA 6.27E−78 P4hb NA 0.38506968 0.369961971 NA 1.73E−74 Tmem176b NA  0.612457008 0.713749974 NA 4.03E−74 Gas6 NA 0.35878079 0.269480866 NA 5.31E−74 Hmgcs1 −0.258009688   0.702526059 −0.387891871  1.33E−13  4.05E−72 Ang 0.315315425  0.644516227 0.599634512 2.44E−79  2.84E−71 Marco NA 0.30539135 NA NA 1.17E−70 Ahsg NA  0.281450293 0.32482682  NA 7.29E−69 Gm12744 NA  0.350643059 NA NA 1.69E−65 Clu NA  0.374886754 0.745288027 NA 3.60E−64 Rbp1 NA  0.396801127 0.32795786  NA 5.19E−64 C1qb NA  0.361309767 0.337494489 NA 2.50E−59 Mki67 NA 0.39305852 NA NA 1.59E−57 Acnat2 NA 0.33547101 NA NA 1.88E−56 Top2a NA 0.33486876 NA NA 1.10E−54 Clec4f NA  0.380337956 0.487336922 NA 1.18E−53 Rpl41 NA  0.444557582 NA NA 1.56E−51 Cdca3 NA  0.286393603 NA NA 1.87E−51 Ifitm2 NA  0.526891524 0.281474354 NA 1.07E−50 Dbi NA  0.360631658 NA NA 9.49E−48 1100001G20Rik NA  0.310291029 NA NA 4.13E−43 Cdc20 NA  0.272554242 NA NA 3.12E−38 Cd302 NA  0.384976006 NA NA 1.82E−37 Csf1r NA  0.284684372 NA NA 3.79E−37 Gstm2 NA  0.466218536 NA NA 3.99E−35 Apoc2 NA  0.517142972 NA NA 6.48E−35 Krt18 NA  0.520354076 NA NA 5.88E−34 Tmsb4x NA  0.347657914 0.341035762 NA 7.53E−31 Dnajc12 NA  0.312907586 NA NA 2.54E−30 Lyz2 NA  0.275390862 0.402735723 NA 1.21E−28 BC048546 NA  0.287060939 NA NA 1.16E−27 Gstm3 −0.470077922   0.793361403 NA 8.30E−17  1.46E−26 Hspa8 NA  0.302152434 NA NA 4.31E−21 Dynll1 NA  0.289016997 NA NA 1.79E−19 Tspan4 NA 0.32084381 NA NA 3.41E−19 Kng2 NA 0.3169695  0.368809413 NA 2.95E−18 2200002D01Rik NA  0.257614019 NA NA 1.71E−17 Cyp51 NA 0.40339747 −0.324000937  NA 4.34E−17 Cyp7a1 NA  0.598824806 NA NA 5.91E−17 Mlec NA  0.400321297 NA NA 1.46E−15 Smc4 NA  0.338338192 NA NA 3.80E−14 Hrg NA  0.270451116 0.58732025  NA 6.86E−14 Sdc1 NA  0.330139692 NA NA 1.43E−12 Hspa5 NA  0.270882455 0.339769129 NA 2.27E−12 Dap NA  0.290008119 0.465257779 NA 3.97E−12 Hsph1 NA  0.345997935 0.425977247 NA 1.02E−10 Mrap NA  0.280974611 NA NA 1.04E−10 Creld2 NA  0.362477611 0.307177214 NA 1.11E−08 Cpox NA  0.294319953 NA NA 2.98E−08 Ebp NA  0.252819864 NA NA 3.69E−07 Fdps NA  0.303232732 −0.254137438  NA 3.91E−06 Ugdh NA  0.260443532 NA NA 4.68E−05 Tmpo NA 0.2573532  NA NA 5.30E−05 Lss NA  0.294433908 NA NA 0.000130068 Akr1d1 NA  0.258293189 NA NA 0.00030931 Snord13 NA  0.408788625 NA NA 0.000327047 Lsr NA  0.262580416 NA NA 0.005770468 Tuba1c NA  0.302939755 NA NA 0.006056912 Caprin1 NA  0.303020851 0.295892842 NA 0.016747307 Atl3 NA  0.255322039 NA NA 0.021123411 Manf NA  0.282950631 NA NA 0.023268676 Avpi1 NA 0.30186919 NA NA 0.101466193 Krt8 NA  0.252276759 NA NA 0.182829207 Sqle NA 0.27714068 NA NA 1 Nucks1 NA  0.271055696 NA NA 1 Lect2 −0.274252442   0.288512824 NA 1.07E−19  1 Oat −0.255537891   0.741679089 NA 4.82E−23  1 Tubb5 NA  0.313824522 NA NA 1 Tubb4b NA 0.28149027 NA NA 1 C4b 0.26668764   0.530516995 0.820022988 4.30E−67  7.45E−90 Vtn NA NA 0.516935534 NA NA Hc NA NA 0.611232959 NA NA Orm3 NA NA 0.517250103 NA NA Serping1 NA NA 0.535830748 NA NA Mpeg1 NA NA 0.541170007 NA NA Cml2 NA NA 0.486040271 NA NA Itih1 NA NA 0.496617676 NA NA Comt NA NA 0.384473508 NA NA Calr NA NA 0.391955529 NA NA Scara5 NA NA 0.285535495 NA NA Cfi NA NA 0.390834066 NA NA Mug2 NA NA 0.536577024 NA NA H2-D1 NA NA 0.433183706 NA NA Lpl NA NA 0.355011922 NA NA Col18a1 NA NA 0.459095159 NA NA Wfdc17 NA NA 0.317329894 NA NA Fetub NA NA 0.425407474 NA NA Serpinf2 NA NA 0.361403772 NA NA H2-Q10 NA NA 0.250632773 NA NA Aldh2 NA NA 0.296492218 NA NA Cyp3a13 NA NA 0.420680082 NA NA F5 NA NA 0.436709177 NA NA Ldhd NA NA 0.387086477 NA NA Pcx NA NA 0.367136085 NA NA Fah NA NA 0.325518495 NA NA Abhd2 NA NA 0.267241512 NA NA Ugt1a1 NA NA 0.370092558 NA NA Cyr61 NA NA 0.302881921 NA NA Pros1 NA NA 0.26812884  NA NA Slc22a7 NA NA 0.307857498 NA NA Ctss NA NA 0.270183132 NA NA P1xnb2 NA NA 0.381208682 NA NA Gne NA NA 0.355262513 NA NA Abcb11 NA NA 0.351857633 NA NA Cpn2 NA NA 0.349996687 NA NA Lgals9 NA NA 0.327550674 NA NA Hamp2 NA NA 0.337201585 NA NA Psap NA NA 0.318472244 NA NA Mafb NA NA 0.356246663 NA NA Cd36 NA NA 0.291074527 NA NA Pdia3 NA NA 0.276156858 NA NA Habp2 NA NA 0.313462443 NA NA Apon NA NA 0.318989204 NA NA Nbr1 NA NA 0.337157409 NA NA Slc25a23 NA NA 0.332651576 NA NA F9 NA NA 0.303980935 NA NA Iigp1 NA NA 0.305889089 NA NA Agt NA NA 0.258205872 NA NA Gns NA NA 0.323226146 NA NA Bsg NA NA 0.273171859 NA NA Scarb1 NA NA 0.32724782  NA NA Sardh NA NA 0.28626336  NA NA Edem1 NA NA 0.301212478 NA NA Abat NA NA 0.305043176 NA NA Dpyd NA NA 0.315635393 NA NA Myo18a NA NA 0.253700048 NA NA St6gal1 NA NA 0.295334926 NA NA Tapbp NA NA 0.265071778 NA NA Ifih1 NA NA 0.264296168 NA NA BC025446 NA NA 0.266911384 NA NA Pcdh1 NA NA 0.265458741 NA NA 1300002K09Rik NA NA 0.30148927  NA NA Plec NA NA 0.267122123 NA NA Uba1 NA NA 0.281371963 NA NA Kynu NA NA 0.28095477  NA NA Rxra NA NA 0.264560061 NA NA Tfr2 NA NA 0.268628506 NA NA Ctnnd1 NA NA 0.252846161 NA NA Fndc3a NA NA 0.273177056 NA NA Adh4 NA NA 0.282357284 NA NA C130074G19Rik NA NA 0.255729195 NA NA Ptprf NA NA 0.27768605  NA NA Osbp19 NA NA 0.270713808 NA NA Vwa8 NA NA 0.262040545 NA NA Plcxd2 NA NA 0.266285463 NA NA Serpina6 NA NA 0.269623074 NA NA Mbl2 NA −0.254854549 0.268002193 NA 5.49E−35 Pid1 NA NA 0.263310286 NA NA Cmah NA NA 0.251319774 NA NA Aldh1b1 NA NA 0.360480753 NA NA Rgn NA NA 0.261094268 NA NA Ifi27 NA NA 0.274586258 NA NA Gulo NA NA 0.282891961 NA NA Slc1a2 NA NA 0.262926395 NA NA Mup3 −0.526410044  −1.423759103 −1.310718039  0 0 Cyb5 −0.71965743  −0.486476838 −0.751689441  0  1.24E−108 mt-Rnr1 −0.872186844  NA −0.844781496  0 NA mt-Rnr2 −0.873557854  −0.51967923  −0.967453486  0  2.69E−141 Mup11 −0.976755523  −1.415092329 −1.769206667  0 0 mt-Nd2 −1.128776891  −1.189410874 −1.350784061  0 0 mt-Nd1 −1.136736863  −1.154630438 −1.543996447  0 0 mt-Nd5 −1.145550707  −1.397897502 −1.49645814  0  1.28E−300 Gm13775 −1.255657303  −1.145210977 −1.171528238  0  3.97E−216 mt-Cytb −1.296043506  −1.378313317 −1.554026854  0 0 mt-Co2 −1.341686736  −1.417328219 −1.39473643  0  5.51E−209 mt-Co1 −1.381307687  −1.399110403 −1.569950123  0 0 Mup5 −1.484560547  −1.768987649 −1.774609558  0  2.08E−280 mt-Nd4 −1.630375247  −1.673140231 −1.953205815  0 0 Mup4 −1.805301681  −1.945646142 −1.909428244  0 0 Mup6 −2.386597202  −2.645373468 −2.588052175  0 0 Mup9 −2.453596744  −2.219144293 −2.520658851  0 0 Mup17 −2.514472885  −2.2696211  −2.382123881  0 0 Mup18 −2.617739049  −2.373348742 −2.585635085  0 0 Mup19 −2.932276479  −3.632170505 −3.348975652  0 0 mt-Co3 −1.233961828  −1.212388388 −1.229639242  1.47E−287  9.73E−175 Cyp2c29 −1.027267705  NA −0.997502622  2.76E−235 NA Mup16 −0.848726713  −0.87654486  −1.245137265  1.76E−222  2.12E−149 Cyp2b10 −1.254972098  −0.995219016 −1.247317124  1.74E−217 1.18E−87 Ankrd55 −1.464696038  −1.950942364 −1.470505577  6.28E−208  2.52E−247 Ugt2b5 −0.423085187  −0.683262994 −0.716336886  8.09E−193  1.47E−190 Apoe −0.26209828  −0.615882949 NA 3.58E−191 0 Gsta3 −0.53784222  −0.579823037 −0.796926805  2.50E−189  2.50E−118 Cyp2c50 −0.763912176  −0.467298435 −0.516529985  8.52E−186 1.54E−52 Mup21 −0.668770594  −1.346645152 −1.637812283  6.47E−176  1.32E−290 Cyp2c54 −0.712859584  −0.542960224 −0.632023168  1.75E−163 2.37E−77 Akr1c6 −0.43492211  −0.501143524 −0.457641734  6.85E−150  1.04E−103 Apoc4 −0.356086407  NA −0.501759591  2.38E−146 NA mt-Atp6 −0.852555757  −0.914635453 −0.875890108  7.98E−137  3.35E−117 Mup15 −1.074409915  −1.364182598 −1.359329494  5.07E−136  2.34E−202 Cyp3a11 −0.251219977  NA −0.803553063  8.18E−135 NA Mgst1 −0.322742924  −0.286240934 −0.36875402  2.50E−131 3.71E−58 Cyp3a25 −0.41051207  −0.34306526  −0.416456818  5.44E−129 2.32E−54 Ces1d −0.385155368  −0.445283361 −1.201503329  2.67E−121 2.43E−81 Mup13 −0.755608269  −0.870972392 −0.875079323  4.35E−116  1.89E−127 Cyp2c37 −0.662335734  −0.412938667 −0.820386118  4.16E−114 1.60E−40 Cyp2a5 −0.938183249  −0.525680085 −0.869524548  8.06E−111 1.48E−38 Serpina3c −0.554657351  −0.589926828 −0.595568461  8.44E−109 8.61E−89 Adh1 −0.295980789  NA NA 3.27E−106 NA Mup8 −0.793731191  −0.829956435 −0.82718199  9.31E−106 3.77E−91 Mup12 −0.589618573  −1.210517374 −1.228078411  2.77E−105  1.10E−243 Aldh1a1 −0.40245097  NA NA 1.39E−102 NA Adck3 −0.482940158  −0.569692886 NA 4.38E−91  6.36E−82 Ahcy −0.375627724  −0.455985571 −0.49011253  1.82E−89  7.46E−73 Cox4i1 −0.288035158  −0.57523009  −0.518813262  5.97E−88   2.44E−141 Hsd3b7 −0.451728474  −0.581642142 NA 3.52E−87  5.15E−93 Mup2 −0.650107006  −0.738721984 −0.72405868  4.29E−84  2.14E−98 Rsp14 −0.346340977  NA −0.607507888  1.86E−83  NA Ugt2b36 −0.287193139  −0.629671114 −0.355795521  5.82E−81   1.10E−145 Acaa1b −0.263859024  −0.742478092 −0.855527427  2.20E−79   8.89E−175 Psen2 −0.419555606  NA NA 1.69E−77  NA Cox6c −0.41128283  −0.517417109 −0.610222852  1.20E−74  4.59E−79 Gm4076 −0.342157966  −0.345826319 −0.342316728  7.98E−74  2.87E−41 Uqcrq −0.316451873  −0.341869458 −0.485354968  1.28E−72  1.11E−51 Igfbp2 −0.348403589  −0.576682095 −0.717832911  3.39E−70   8.96E−103 Rnf125 −0.463320018  −0.423361675 −0.310633092  9.28E−70  1.00E−57 mt-Nd6 −0.515107457  −0.560268731 −0.685505467  1.57E−69  1.14E−72 Rps2 −0.44250848  −0.269321392 −0.474519664  4.24E−69  2.20E−20 Hsd3b5 −0.587528886  −0.886463454 −0.506259792  1.00E−67   3.58E−129 Cyp1a2 −0.481919967  NA −0.284567418  3.86E−66  NA Rpl13a −0.314606263  NA −0.480174283  7.45E−64  NA Rps27l −0.361138678  −0.377566144 −0.64582348  1.30E−60  7.98E−50 Pon1 −0.302819466  −0.42825679  −0.32604762  2.10E−60  1.97E−64 Gm20594 −0.559577825  −0.573781187 −0.496964367  4.48E−60  1.21E−52 Mvd −0.327327327  NA NA 2.22E−59  NA Sparcl1 −0.253616986  −0.253616986 −0.253616986  3.78E−57  5.97E−29 Malat1 −0.652623643  NA −0.41172143  6.64E−56  NA Cyp8b1 −0.364571013  −0.565483524 −0.599290325  3.21E−55  1.09E−90 Ugt2b34 −0.290735843  NA −0.500802828  1.26E−52  NA Hacl1 −0.332899987  NA −0.294916761  4.71E−52  NA Zfp683 −0.421689112  −0.421689112 −0.421689112  1.10E−47  7.40E−24 Oaf −0.333766768  NA NA 3.11E−47  NA Cth −0.308847665  −0.332234114 −0.339209942  6.91E−47  4.36E−37 Ndufb11 −0.36792318  −0.398618793 −0.479044618  4.92E−46  7.18E−49 Esd −0.302906103  −0.381539462 −0.338909518  9.71E−44  1.94E−49 Mpc2 −0.268047152  NA −0.39520967  4.77E−43  NA Ubc −0.273242853  NA NA 3.58E−41  NA Hebp1 −0.313009472  −0.297464234 −0.274169133  1.26E−40  8.29E−32 Gm5096 −0.399548106  −0.336704156 −0.350534749  4.99E−39  1.27E−33 Oaz1 −0.339004868  −0.426286153 −0.327014451  2.14E−37  1.27E−51 Cox7b −0.304638563  −0.386524219 −0.650085753  6.26E−37  1.05E−43 Cyp2c55 −0.316565473  NA −0.347841415  6.52E−37  NA Inmt −0.308364158  −0.502414474 −0.679790467  9.17E−37  1.61E−65 Cyp2e1 −0.301497571  −0.298608744 0.296899706 4.23E−36  2.45E−19 Clpx −0.306093278  −0.410840842 −0.250587235  6.23E−36  1.11E−53 Ndufb6 −0.311202811  −0.479162745 −0.518384931  1.04E−35  4.11E−68 Hist1h1c −0.331045753  NA NA 5.78E−33  NA Elovl3 −0.25229278  −0.812250701 −0.924845607  2.20E−32   1.80E−150 Gm10250 −0.30688429  −0.304478582 −0.336847064  1.80E−31  5.57E−32 Arl4d −0.328520283  −0.288941612 NA 5.36E−30  3.05E−26 Cml1 −0.277339974  −0.47269345  NA 2.15E−27  5.55E−63 Hint2 −0.299309844  −0.373773572 −0.33360366  6.95E−27  2.60E−44 Aqp8 −0.331182913  −0.359788885 −0.273149234  1.22E−25  8.19E−45 Ndufa6 −0.25272382  −0.330965466 −0.418444742  8.39E−24  3.11E−32 Gm9843 −0.343302667  −0.298882573 −0.396322103  1.60E−22  7.79E−23 Atp5h −0.351854327  −0.352362982 −0.555498653  4.84E−19  7.17E−29 Dcxr −0.271339616  NA NA 1.59E−18  NA Cebpa −0.260692112  −0.481611184 NA 6.82E−18  2.92E−66 Cyp4a10 −0.289941035  −0.698160085 −0.453214203  4.30E−17  2.61E−98 Sigmar1 −0.282364617  NA NA 5.67E−17  NA Nr1i3 −0.317940692  NA NA 1.11E−16  NA Ppp2r5a −0.263513608  −0.315098874 −0.281895906  3.57E−15  3.37E−36 Hhex −0.283483187  NA NA 9.95E−15  NA Rpl14 −0.261157069  NA −0.357060958  2.50E−13  NA Tprkb −0.254084951  NA NA 1.31E−12  NA Cyp3a59 −0.263118105  NA NA 3.34E−11  NA Rps18 −0.269206741  NA −0.415076007  5.39E−06  NA Ftl1 −0.346327339  −0.259151442 −0.347806606  3.34E−05  1.49E−07 Ubb −0.263773933  NA NA      0.0138701 NA Mup1 −0.490972296  −0.62326727  −0.882906956      0.022977 1.11E−33 Mup7 −0.293978105  −0.847726732 −0.844127621      0.067179  2.63E−114 Gm24245 −0.254157233  −0.264578368 NA 1 3.33E−13 Mup14 −0.340890047  −0.497427273 −0.741008747  1 2.38E−27 Apoa2 NA −0.615981195 −0.42773886  NA 0 Mup20 NA −1.237817166 −1.081531043  NA 0 Car3 NA −1.292191881 −1.168630683  NA  2.01E−301 2810007J24Rik NA −1.093998287 −0.337772907  NA  2.63E−273 Tdo2 0.25156007  −0.736504592 −0.283022598  2.99E−135  6.44E−267 Rbp4 NA −0.580599925 −0.451760058  NA  1.32E−259 Fabp1 NA −0.542167351 −0.826491833  NA  8.21E−214 Hsd11b1 NA −0.998666341 −0.332361427  NA  3.95E−209 Ces3a NA −0.721008165 NA NA  1.41E−206 Hmgcs2 NA −0.664269004 NA NA  6.01E−206 Serpina1d NA −0.586852756 NA NA  5.86E−199 Selenbp2 NA −0.857199402 −0.354512086  NA  9.70E−194 Hrsp12 NA −0.800669662 −0.395396316  NA  1.58E−182 Ces3b NA −0.819558687 NA NA  6.86E−161 Cyp2d9 NA −0.616676578 −0.3250388    NA  8.72E−151 Retsat NA −0.784380771 −0.847260321  NA  5.47E−148 Ugt2b1 NA −0.722102286 −0.261758027  NA  5.69E−140 Serpina3k NA −0.279762031 −0.298266533  NA  3.34E−138 H2-K1 NA −0.596584494 NA NA  1.74E−137 Cyp2f2 0.275177176 −0.887034648 NA 2.08E−44   5.25E−136 Pigr NA −0.661452   NA NA  1.08E−134 Rdh7 NA −0.496910675 NA NA  5.58E−132 Apoa1 NA −0.336207866 −0.411233725  NA  5.20E−127 Apoh NA −0.417935459 NA NA  3.98E−126 Aadac NA −0.747342823 −0.466442698  NA  6.76E−122 Ephx2 NA −0.570800981 −0.398908219  NA  1.49E−121 Gpx1 NA −0.321984135 NA NA  2.36E−120 Alb NA −0.427719117 NA NA  2.56E−117 Otc NA −0.584972427 NA NA  1.50E−116 Apoa5 0.30259839  −0.470514722 NA 5.32E−149  3.16E−115 Mug1 NA −0.497189268 NA NA  3.61E−105 Acsl1 NA −0.568030382 −0.417030322  NA  3.63E−104 Cyp4v3 NA −0.600614165 NA NA  1.46E−101 Slco1a1 NA −0.632477905 −0.542407867  NA  5.52E−101 Cfhr2 NA −0.630617674 −0.428849834  NA 7.59E−98 B2m NA −0.430851295 NA NA 2.11E−97 Khk NA −0.530150378 NA NA 8.89E−91 Apoc1 NA −0.31073779  NA NA 1.04E−90 Uox NA −0.480422343 NA NA 1.42E−89 Rarres2 NA −0.492013911 NA NA 1.76E−89 Serpina12 NA −0.612367467 −0.404557025  NA 7.52E−89 Serpinc1 NA −0.333556351 NA NA 1.38E−87 Ugt2a3 NA −0.54739922  −0.457903234  NA 2.33E−87 Serpinf1 NA −0.506061854 NA NA 3.06E−85 Ttr NA −0.286138394 NA NA 3.87E−82 C8g NA −0.455638561 NA NA 2.41E−80 Serpina1a NA −0.35536875  −0.295262554  NA 3.38E−75 Serpina1b NA −0.294480791 NA NA 1.99E−74 Serpina1e NA −0.308360801 −0.72519719  NA 1.15E−71 Etnppl NA −0.549126978 −0.566620392  NA 2.68E−71 1500017E21Rik NA −0.517930222 NA NA 1.93E−69 Atp5f1 NA −0.460709866 −0.428496879  NA 1.11E−68 Ces1f NA −0.45903711  −0.533638921  NA 9.66E−67 Cyp4a12a 0.259776426 −0.4760363  NA 1.18E−52  1.00E−65 Baat NA −0.445833101 −0.265815179  NA 1.01E−65 Fabp2 NA −0.488533591 −0.527186942  NA 5.45E−64 Serpina1e NA −0.279835146 NA NA 1.24E−63 Sod1 NA −0.277853669 −0.483374172  NA 1.68E−63 Cdo1 NA −0.343333854 NA NA 2.05E−63 Ech1 NA −0.414674796 −0.504022226  NA 2.57E−62 Insig2 NA −0.447606183 −0.275363349  NA 4.77E−62 Cox6a1 NA −0.390617907 −0.275276508  NA 1.67E−61 Azgp1 NA −0.286918536 NA NA 1.16E−60 Ces1c NA −0.274525359 NA NA 5.85E−60 Pah NA −0.379853874 NA NA 8.65E−60 Lipc NA −0.423055461 NA NA 3.19E−59 Dio1 NA −0.469732353 NA NA 9.15E−59 Aox3 0.275388909 −0.429460462 NA 1.72E−66  1.23E−58 Gstm1 NA −0.448355325 −0.35224443  NA 3.06E−58 Slc27a5 NA −0.374625102 NA NA 1.08E−57 Amy1 NA −0.441174   NA NA 1.40E−57 Tmem205 NA −0.363762607 NA NA 6.01E−57 Cyp2a12 NA −0.396631721 NA NA 6.96E−57 Angptl3 NA −0.315601765 −0.529458826  NA 1.53E−55 Cyp7b1 NA −0.438158056 NA NA 1.37E−54 Hpd NA −0.317943335 NA NA 2.00E−54 Ugp2 NA −0.394209561 NA NA 6.59E−54 Ndufa4 NA −0.4035957  −0.512722876  NA 1.02E−52 Nudt7 NA −0.566043759 NA NA 9.48E−52 Slc10a1 NA −0.395488081 −0.273026083  NA 8.15E−51 Scp2 0.279911381 −0.319519472 NA 5.16E−159 1.15E−50 Sco2 NA −0.395951512 −0.250104753  NA 1.04E−49 Cyp2d10 NA −0.325332653 −0.26237727  NA 3.76E−49 Chchd2 NA −0.369755887 −0.518624159  NA 1.70E−48 Idh3b NA −0.360516268 NA NA 4.19E−48 Bckdha NA −0.404702898 NA NA 2.27E−47 Glo1 NA −0.379233492 −0.317338548  NA 3.51E−47 Sdhb NA −0.357362255 NA NA 2.51E−46 Cat NA −0.286016441 NA NA 1.00E−45 Ces1e NA −0.356936678 −0.375733204  NA 2.06E−45 Cox5b NA −0.393691854 −0.373464063  NA 3.39E−45 Atp5g3 NA −0.302277876 −0.357248453  NA 2.31E−44 Itm2b NA −0.261048932 NA NA 4.20E−44 Etfdh NA −0.33708519  NA NA 1.81E−43 Gsto1 NA −0.368935961 NA NA 5.15E−43 Hsd3b3 NA −0.347460551 NA NA 3.82E−42 Slc27a2 NA −0.305294922 NA NA 2.23E−41 Hsd17b6 NA −0.36218325  −0.364685233  NA 2.58E−41 Abcd3 NA −0.326838469 NA NA 1.45E−40 Mdh1 NA −0.329025797 NA NA 2.04E−40 Prdx4 NA −0.378024564 −0.339424675  NA 3.39E−40 Hsd17b13 0.351593878 −0.376251609 NA 1.14E−64  5.32E−40 Proc NA −0.319776879 NA NA 1.66E−39 Agxt NA −0.303827932 NA NA 1.79E−39 Gls2 0.296143664 −0.353616749 NA 1.09E−57  2.16E−39 Ugt2b38 NA −0.250921219 NA NA 1.20E−38 Ndufb9 NA −0.291910914 −0.483703094  NA 2.15E−38 Rabac1 NA −0.342063679 −0.275369587  NA 3.25E−38 Slc22a30 NA −0.331870745 −0.25736876  NA 7.77E−38 Etfa NA −0.33793403  NA NA 8.07E−38 Atp5j NA −0.302644835 −0.415380683  NA 4.96E−37 Uqcrfs1 NA −0.335765197 NA NA 5.60E−37 Cyp27a1 NA −0.326228094 NA NA 1.46E−36 Hal NA −0.304647432 NA NA 3.02E−36 Sar1b NA −0.301891484 −0.422088437  NA 4.44E−36 Aldh6a1 NA −0.30870904  NA NA 4.64E−36 Il1rap NA −0.302807638 NA NA 1.94E−35 S100a1 NA −0.355544479 NA NA 2.21E−35 Creg1 NA −0.258963412 −0.480113825  NA 2.90E−35 1300017J02Rik NA −0.308343818 NA NA 1.20E−34 Acat1 NA −0.290805818 NA NA 1.81E−34 Pklr 0.25984035  −0.283149611 NA 4.04E−64  5.43E−34 Dpys NA −0.313405671 NA NA 8.84E−34 Aadat NA −0.325731706 NA NA 9.13E−34 Cd81 NA −0.30883572  NA NA 1.50E−33 Ndufc2 NA −0.370889898 −0.371342649  NA 1.56E−33 Bphl NA −0.299478155 NA NA 1.70E−33 Qdpr NA −0.316595182 NA NA 1.80E−33 Gsta2 NA −0.284180552 NA NA 4.56E−33 Acsm3 NA −0.280708005 NA NA 5.27E−33 Cyp2d26 NA −0.270278674 NA NA 2.04E−32 Cyp2c44 NA −0.312764543 NA NA 2.09E−32 Hagh NA −0.288430674 −0.398106396  NA 2.99E−32 Ces2a NA −0.288140076 −0.619093582  NA 4.30E−32 Gas5 NA −0.298417518 NA NA 6.31E−32 Uqcrb NA −0.339504918 −0.359656695  NA 1.34E−31 Gm4788 NA −0.297042332 NA NA 1.49E−31 Slc2a2 NA −0.291267847 NA NA 2.49E−31 Cela1 NA −0.252611197 NA NA 1.03E−30 Hgd NA −0.273998205 NA NA 2.46E−30 1110008F13Rik NA −0.284458511 −0.327482854  NA 3.77E−30 Csad NA −0.308703065 −1.214863323  NA 4.35E−30 Gabarapl1 NA −0.297156374 NA NA 2.02E−29 Eci1 NA −0.292606814 −0.31335345  NA 4.47E−29 Amdhd1 NA −0.272469871 NA NA 8.10E−29 Uqcrh NA −0.290259964 −0.483113531  NA 1.52E−28 0610011F06Rik NA −0.28593883  NA NA 3.51E−28 Ftcd NA −0.299187456 NA NA 5.47E−28 Cyp4f14 NA −0.283565035 NA NA 6.47E−28 Ttc39c NA −0.289612311 NA NA 2.34E−27 Ndufv1 NA −0.256865664 NA NA 2.43E−27 Pdhb NA −0.271619421 NA NA 5.48E−27 Hsd17b11 NA −0.272884574 NA NA 8.36E−27 Fcgrt NA −0.270945405 NA NA 1.81E−26 Lyrm5 NA −0.251171881 NA NA 3.08E−26 Bnip3 NA −0.275946132 −0.272700001  NA 3.10E−26 Pygl NA −0.25405228  NA NA 1.29E−25 C8b NA −0.251084368 NA NA 1.50E−25 Atp5j2 NA −0.255051714 −0.409576712  NA 2.55E−25 Fxyd1 NA −0.273422293 NA NA 2.95E−25 Nit2 NA −0.255321274 NA NA 6.79E−25 Sdha NA −0.286156431 NA NA 7.96E−25 Pccb NA −0.266663529 NA NA 8.00E−25 Park7 NA −0.270929309 NA NA 9.02E−25 Cmbl NA −0.265365994 NA NA 9.66E−25 Ces2e NA −0.272708804 NA NA 8.71E−24 Cebpb NA −0.306330499 −0.267669957  NA 1.73E−23 Pbld1 NA −0.264627734 NA NA 2.23E−23 Adipor2 NA −0.252551165 NA NA 1.11E−22 Ephx1 NA −0.261640077 −0.332038055  NA 1.26E−22 C6 NA −0.255102014 NA NA 2.04E−21 Rn7sk NA −0.276399379 NA NA 6.19E−14 Hint1 NA NA −0.487016283  NA NA Gstp1 NA NA −0.671664785  NA NA Gnmt NA NA −0.288175489  NA NA Sc4mol NA NA −0.519568919  NA NA Prdx1 NA NA −0.353764247  NA NA Rpl32 NA NA −0.498592915  NA NA Uqcr11 NA NA −0.368070557  NA NA Cox7a2 NA NA −0.441101884  NA NA Rps3 NA NA −0.339903958  NA NA Ndufb8 NA NA −0.389897205  NA NA Etfb NA NA −0.270014172  NA NA Leap2 NA NA −0.404792721  NA NA Uqcr10 NA NA −0.382321788  NA NA Akr1c19 NA NA −0.38253326  NA NA Ddt NA NA −0.345838673  NA NA Eef1b2 NA NA −0.367328377  NA NA Chchd10 NA NA −0.28090926  NA NA Rps24 NA NA −0.386464837  NA NA Acot1 NA NA −0.299327096  NA NA Cyp3a44 NA NA −0.297417766  NA NA Ndufb4 NA NA −0.331687642  NA NA Sdhd NA NA −0.302302961  NA NA Rps5 NA NA −0.25674004  NA NA Ndufb2 NA NA −0.336855533  NA NA Blvrb NA NA −0.351075319  NA NA Ndufs6 NA NA −0.341035035  NA NA Cnbp NA NA −0.286746587  NA NA Cyp4a14 NA NA −0.31778609  NA NA Txn1 NA NA −0.277353299  NA NA Rpl36al NA NA −0.331844566  NA NA Gadd45b NA NA −0.301158726  NA NA G0s2 NA NA −0.269113384  NA NA Ssr4 NA NA −0.283161199  NA NA Minos1 NA NA −0.308403636  NA NA Ndufa2 NA NA −0.308306345  NA NA Tmem243 NA NA −0.275109242  NA NA Rps21 NA NA −0.316866281  NA NA Ndufa5 NA NA −0.310280044  NA NA Tubb2a NA NA −0.260491764  NA NA Akr1c14 NA NA −0.280169437  NA NA Atp5o NA NA −0.268645357  NA NA Psmb1 NA NA −0.271574562  NA NA Rps9 NA NA −0.30861002  NA NA Nme1 NA NA −0.291609359  NA NA Ndufb5 NA NA −0.274484363  NA NA Psma6 NA NA −0.281709731  NA NA Rplp1 NA NA −0.274821325  NA NA Fam162a NA NA −0.280519821  NA NA 4931406C07Rik NA NA −0.28178071  NA NA Sc5d NA NA −0.274286355  NA NA Timm13 NA NA −0.266267617  NA NA Ndufs4 NA NA −0.299960018  NA NA Selk NA NA −0.279248941  NA NA Mrps18c NA NA −0.27427115  NA NA Rpl13 −0.314606263  NA −0.282418264  7.45E−64  NA Rps8 NA NA −0.279845708  NA NA Rps15 NA NA −0.324542895  NA NA N1rp12 NA NA −0.269307598  NA NA Timm8b NA NA −0.25098905  NA NA Dhrs4 NA NA −0.268862728  NA NA Rps10 NA NA −0.252659935  NA NA Rpl34 NA NA −0.264586248  NA NA Hspe1 NA NA −0.257910168  NA NA Usmg5 NA NA −0.28365494  NA NA Rpl26 NA NA −0.264487941  NA NA Rps19 NA NA −0.25849266  NA NA ID PH120p avg_logFC p_val_adj Saa2 0 4.43818759 0 Mt1 0 2.610854994 0 Mt2 0 2.6060431 0 Saa1 0 3.650785996 0 Steap4  1.31E−284 1.890015167 0 Serpina3n 0 1.759758939 0 Lcn2 0 2.39758181 0 Lpin1 4.53E−64 1.327657625 0 n-R5-8s1 0 1.289598504 0 Igfbp1 1.15E−78 1.288789902 0 Cxcl1 NA 1.230398019 0 Scd1  3.71E−204 1.081676999 0 Gm26924 0 1.445355764 0 Il1r1  4.69E−177 0.998168131 0 Fga 0 1.039432587 0 Gm24601 0 0.924568273 0 Nnmt 6.69E−98 0.901052904 0 Itih4 0 1.18011817 0 St3gal5 NA 0.882761517 0 Tacc2 NA 0.877623973 0 Lrg1 0 1.260509735 0 Fam134b NA 0.865578177 0 Tat  3.93E−194 0.857965136 0 Saa4 0 1.158596154 0 Thrsp 4.31E−54 0.836598219 0 Slc39a14  1.16E−108 0.831584936 0 Lars2 0 1.419129056 0 Fgg 0 0.809322713 0 Slc38a2 1.34E−44 0.797899442 0 Serpina3m 2.80E−48 0.779052745 0 Hp 0 1.584889895 0 Fgb 0 0.739519125 0 Gm15564 0 1.485885928 0 Serpina10  1.35E−230 0.871044179 0 Plin2 NA 0.720463076 0 Fmo5 5.95E−73 0.690160801 0 Fkbp5 NA 0.663304836 0 Slc25a47 NA 0.635928777 0 Mat1a  2.90E−246 0.623734998 0 Acox1 1.80E−68 0.540022158 0 Aldob NA 0.490200848 0 C3 0 1.071950932 0 B3galt1 8.61E−40 0.788734938  3.52E−301 Fn1 0 1.018772906 0 Hnf4a  3.08E−110 0.644195253  5.68E−290 Btg2 2.69E−68 0.772686832  7.24E−290 H3f3b NA 0.755567107  4.44E−288 Aass 3.70E−47 0.705615345  1.07E−286 Sephs2  1.86E−182 0.618707003  1.06E−281 Cldn14 NA 0.511583526  4.32E−281 Rcan1 NA 0.509239866  4.58E−279 Hspb8  4.23E−133 0.667847253  9.19E−267 Arhgef26 4.52E−47 0.568544702  4.92E−265 Slc7a2 2.68E−62 0.622326529  6.74E−265 Pfkfb3 NA 0.426580733  3.82E−264 Pck1  8.65E−210 0.495042924  4.86E−264 Errfi1 NA 0.500850526  7.43E−262 Gjb2 1.88E−70 0.639507436  9.92E−255 Snx10 NA 0.558244633  1.59E−251 Bcl3 NA 0.419650143  3.05E−251 Hpx 0 1.443685235 0 Bach1 NA 0.533237374  5.54E−247 Tifa  4.02E−144 0.392339477  3.72E−241 2010003K11Rik NA 0.372219971  1.06E−239 Pzp 0 0.636851805 0 Tiparp NA 0.489122153  7.07E−236 Rapgef4 NA 0.588317735  4.64E−233 Mup10  4.03E−105 0.428268029  1.14E−231 Egfr  4.26E−199 0.65440823  5.47E−228 mmu-mir-6236  5.14E−284 1.257248389  5.14E−284 Etnk2 NA 0.592353201  7.87E−221 Mfsd2a NA 0.496351884  1.64E−219 Txnip NA 0.552612237  1.04E−218 Arg1 NA 0.381616351  2.23E−218 Gpt2 NA 0.533331785  3.67E−218 Slc25a25 2.18E−84 0.544465891  2.55E−217 Actb NA 0.456981443  2.15E−210 Xbp1 NA 0.539986  1.34E−208 Upp2 NA 0.541753512  2.02E−206 Fbf1 NA 0.298573909  4.53E−206 Plin5 NA 0.489257529  1.01E−205 Plk3 NA 0.488016367  8.22E−205 Trib1 NA 0.581754281  1.57E−204 Mtss1 1.12E−54 0.552137981  2.07E−204 Klf6 NA 0.3616937  8.00E−203 Itih3 0 1.223022315 0 Slc10a2 NA 0.30563824  6.54E−197 Sdc4 2.10E−74 0.43560504  2.70E−193 Atf3 3.11E−27 0.597274889  1.23E−191 Ptp4a1 NA 0.393137367  6.10E−190 Prg4  8.36E−244 0.810835665  8.36E−244 Rgs16 NA 0.438105488  3.55E−188 Gpcpd1 NA 0.53780646  5.36E−188 Rhob NA 0.37207281  4.39E−187 Glul       0.000261488 1  1.01E−186 Fam35a NA 0.470461753  7.67E−186 Klf10 NA 0.304779554  1.06E−185 Egr1 3.36E−20 0.620480469  7.27E−185 Apcs  5.94E−275 2.049485412 0 Shb NA 0.430613558  4.03E−182 Orm1 0 1.823760769 0 Fgl1 0 1.561880768 0 1810055G02Rik NA 0.382584093  7.73E−175 Stat3 1.75E−98 0.483904634  3.58E−174 Abca1 2.16E−52 0.50506234  3.19E−172 Igfbp4  1.27E−128 0.411174683  6.69E−171 Got1 7.35E−48 0.542891511  7.82E−171 Cdkn1a NA 0.449325471  7.06E−169 Apob  4.63E−151 0.505397578  8.05E−169 Gfra1 NA 0.474694426  4.73E−168 Ivns1abp NA 0.46254094  9.44E−168 Slc41a2  4.36E−127 0.441321771  2.22E−166 Slc25a51 NA 0.372157664  1.11E−164 Myo1e NA 0.399456672  7.83E−162 Gm23935  1.38E−297 1.207244314  1.38E−297 Bhlhe40 1.23E−69 0.403249298  3.04E−158 Ddx3x NA 0.47100162  1.36E−155 Tmem87b NA 0.288330587  8.72E−155 Dak NA 0.481947664  1.71E−153 Slc25a22 NA 0.390931532  7.19E−153 Fasn NA 0.467168076  2.55E−152 Fh1 NA 0.471428771  7.97E−152 Rnf103 NA 0.438540394  1.39E−149 Sds NA 0.787094904  5.50E−149 B4galt1 NA 0.321380868  4.77E−146 Cps1 8.39E−77 0.336429448  1.19E−145 Atp1b1 NA 0.424801231  1.32E−145 Jmjd1c NA 0.39612601  1.05E−144 Gm26917 7.15E−51 0.475554164  2.42E−144 Junb NA 0.458500682  1.57E−143 4933426M11Rik NA 0.28624304  1.78E−142 Pik3r1 NA 0.389193614  1.89E−142 D10Wsu102e NA 0.256022156  1.03E−141 Hyou1 3.39E−91 0.496156079  3.60E−141 Glud1 1.30E−69 0.359099708  1.11E−139 Cpt1a 1.19E−34 0.42860734  3.31E−139 Epas1 NA 0.38425941  2.12E−138 Jun NA 0.479246114  2.64E−135 Mbd1 NA 0.348094524  2.44E−134 Rnd3 NA 0.285147682  4.66E−134 Litaf NA 0.396007707  2.34E−132 Ptpn1 NA 0.268263225  6.92E−130 Bcl2l1 NA 0.280315334  1.17E−128 Grn 1.12E−47 0.403315761  3.44E−128 Tns1 NA 0.33981795  4.58E−128 Slc25a15 4.09E−89 0.402049896  6.99E−128 Gadd45g NA 0.392031882  7.78E−128 Wbp1l NA 0.409138156  1.29E−127 Foxa3 NA 0.307992015  2.28E−126 Myh9  2.83E−141 0.631035657  2.83E−141 Fos NA 0.524733327  3.55E−125 Id2 NA 0.430147785  5.03E−124 Itih2 NA 0.336714211  1.56E−122 Plg 0 0.596524395 0 Qsox1  2.24E−241 0.725062115  2.24E−241 Ccnl1 NA 0.341338448  1.67E−120 Eef1a1 NA 0.340768186  6.14E−119 Ier2 NA 0.452598264  1.60E−118 Elovl6 NA 0.37962641  5.92E−117 Nedd4l NA 0.271827098  1.51E−116 Ppip5k2 NA 0.30299148  3.63E−115 Epb4.1 NA 0.349430673  1.93E−113 Cfh 0 0.83288399 0 Ulk1 NA 0.297841785  5.13E−113 Ell2 NA 0.371745977  9.30E−113 Tnfrsf1a 1.90E−43 0.346845029  3.42E−112 Eif4g2 8.07E−39 0.384302798  2.51E−110 Ly6e 0 1.093957206 0 Il6ra NA 0.251696836  2.93E−108 Lpgat1 1.05E−64 0.400787984  1.25E−107 Fads2 NA 0.323744791  4.78E−106 Atl2 NA 0.321873809  5.02E−106 Dst NA 0.329905553  7.40E−105 Jak1 NA 0.362766687  2.44E−103 Nfil3 NA 0.338730712  5.23E−103 Elovl5 NA 0.382267188  1.08E−102 Mgll NA 0.321840174  6.61E−101 Sult1a1 NA 0.371023537 2.67E−99 Man2a1 1.19E−46 0.369999358 3.60E−98 Eef2 1.02E−72 0.321705764 1.70E−97 Aff4 NA 0.344186222 7.00E−97 Palmd NA 0.284673594 9.43E−97 Zfp36 NA 0.407014847 1.05E−96 Eif1a NA 0.295219945 7.80E−96 Slc3a1 2.59E−55 0.381791335 1.93E−94 Ifitm3  2.86E−148 0.506857449  2.86E−148 Atp2a2 4.42E−29 0.350363266 8.21E−94 Nop58 NA 0.257566653 1.12E−93 Enpp2 NA 0.316882991 4.48E−93 Gm2a NA 0.341145926 6.61E−93 Cyb5r3 NA 0.337684684 1.90E−92 Apoa4 NA 1.186863065  3.01E−137 Aldh1l1  5.65E−221 0.564932962  5.65E−221 Eci2 NA 0.288159513 5.23E−88 Slc38a3 4.90E−80 0.353500212 1.28E−87 Dusp1 NA 0.300628481 1.26E−86 Igf1 NA 0.277138761 2.86E−86 Serinc3 NA 0.293964974 2.71E−85 Tgm2 2.52E−59 0.37123494 5.50E−85 C8a 3.00E−96 0.404198047 3.00E−96 Txnrd1 NA 0.314979852 3.22E−84 Asl NA 0.297673772 1.76E−83 Por NA 0.290745567 3.93E−83 Sec14l4 NA 0.285169227 5.54E−83 Uroc1 3.99E−76 0.459322934 1.13E−82 Lrp6 NA 0.270740438 1.18E−82 Atf6 NA 0.280521162 1.55E−82 Ddi2 NA 0.302519699 2.71E−82 Dstn NA 0.271381717 2.90E−82 Id3 NA 0.399520373 9.94E−82 H6pd  1.01E−111 0.491965789  1.01E−111 Xdh 1.44E−68 0.373181784 8.54E−81 Tmed5 NA 0.296018777 1.36E−80 G6pc NA 0.341403933 2.15E−80 Mttp NA 0.296651415 2.14E−79 Angptl4 NA 0.315315425 2.44E−79 Nrp1 NA 0.268796793 7.49E−79 Fgf1 NA 0.287983029 7.97E−79 Prox1 NA 0.31520499 3.03E−77 Gck NA 0.260705425 6.82E−77 Picalm NA 0.276902165 1.27E−76 Lbp  1.44E−171 0.656662588  1.44E−171 Azin1 NA 0.268891169 7.99E−76 Ddx5 NA 0.251675045 3.02E−75 Cpb2  3.34E−100 0.403790403  3.34E−100 Il6st 3.35E−58 0.382881893 3.02E−73 Rmnd5a NA 0.273473023 5.48E−73 Trp53inp1 NA 0.269278401 1.01E−72 Ctsb  4.51E−149 0.553974491  4.51E−149 Acsl4 NA 0.273275871 5.43E−70 Elovl2 NA 0.285038606 2.60E−69 Iqgap2 NA 0.283192936 5.91E−69 Lrp1  2.17E−231 0.914046975  2.17E−231 Arhgef12 1.26E−32 0.304865834 1.49E−67 Pim3 NA 0.280137371 3.27E−67 C4bp  1.14E−148 0.530516995  1.14E−148 Lrpprc NA 0.257016288 6.41E−67 Atp1a1 NA 0.261718912 2.96E−65 Copa 4.75E−40 0.294256247 1.69E−64 Acly NA 0.287663867 4.67E−64 Rcl1 NA 0.273905375 1.37E−63 Alas1 2.11E−43 0.423999349 6.82E−63 Kmo 4.54E−49 0.305370487 2.45E−62 Ppp1r3b NA 0.259418401 1.58E−61 Zfp36l1 NA 0.271823824 4.54E−61 Efna1 2.85E−25 0.268455179 2.55E−60 Ctsl NA 0.256520866 1.56E−59 Ptplad1 NA 0.255273084 2.04E−59 Hdlbp 2.52E−71 0.394030651 2.52E−71 Pnpla7 NA 0.251226201 4.93E−58 Fads1 NA 0.267264464 2.35E−57 Nedd4 NA 0.259978699 7.35E−56 Mtus1 4.23E−49 0.385483144 2.92E−54 Cyp2c70  6.40E−150 0.511802822  6.40E−150 Brd2 NA 0.258446853 8.84E−51 Saa3 NA 2.199786317 0 Orm2 0 2.405086745 0 Ambp  6.84E−288 0.496213815  6.84E−288 Trf NA 0.436833817  1.60E−148 Rnase4 0 1.031156304 0 Prtn3  4.48E−205 0.350182853  4.48E−205 Fam25c NA 0.96762143  2.76E−118 Cp  5.81E−290 0.655511152  5.81E−290 Dhcr24  1.45E−130 0.759730578  1.45E−130 Kng1 0 0.546835494 0 Csf2ra NA 0.342712543  3.48E−100 D17H6S56E-5 NA 0.560241333 2.13E−95 Cxcl14 NA 0.268462966 7.87E−89 Hsp90ab1 1.17E−94 0.455851506 1.17E−94 Tmem176a  1.27E−190 0.675060004  1.27E−190 Isyna1 2.67E−89 0.320415943 2.67E−89 Cd5l  4.68E−138 0.49371428  4.68E−138 Ccnd1 NA 0.385849227 6.27E−78 P4hb  1.31E−132 0.38506968  1.31E−132 Tmem176b  3.22E−226 0.713749974  3.22E−226 Gas6  1.89E−110 0.35878079  1.89E−110 Hmgcs1 6.89E−53 0.702526059 4.05E−72 Ang  3.32E−128 0.644516227  3.32E−128 Marco NA 0.30539135 1.17E−70 Ahsg  3.27E−222 0.32482682  3.27E−222 Gm12744 NA 0.350643059 1.69E−65 Clu 0 0.745288027 0 Rbp1  1.56E−104 0.396801127  1.56E−104 C1qb  6.35E−100 0.361309767  6.35E−100 Mki67 NA 0.39305852 1.59E−57 Acnat2 NA 0.33547101 1.88E−56 Top2a NA 0.33486876 1.10E−54 Clec4f  1.73E−119 0.487336922  1.73E−119 Rpl41 NA 0.444557582 1.56E−51 Cdca3 NA 0.286393603 1.87E−51 Ifitm2 8.05E−44 0.526891524 1.07E−50 Dbi NA 0.360631658 9.49E−48 1100001G20Rik NA 0.310291029 4.13E−43 Cdc20 NA 0.272554242 3.12E−38 Cd302 NA 0.384976006 1.82E−37 Csf1r NA 0.284684372 3.79E−37 Gstm2 NA 0.466218536 3.99E−35 Apoc2 NA 0.517142972 6.48E−35 Krt18 NA 0.520354076 5.88E−34 Tmsb4x 1.30E−70 0.347657914 1.30E−70 Dnajc12 NA 0.312907586 2.54E−30 Lyz2 3.33E−93 0.402735723 3.33E−93 BC048546 NA 0.287060939 1.16E−27 Gstm3 NA 0.793361403 1.46E−26 Hspa8 NA 0.302152434 4.31E−21 Dynll1 NA 0.289016997 1.79E−19 Tspan4 NA 0.32084381 3.41E−19 Kng2 1.89E−81 0.368809413 1.89E−81 2200002D01Rik NA 0.257614019 1.71E−17 Cyp51 5.74E−31 0.40339747 5.74E−31 Cyp7a1 NA 0.598824806 5.91E−17 Mlec NA 0.400321297 1.46E−15 Smc4 NA 0.338338192 3.80E−14 Hrg  3.97E−209 0.58732025  3.97E−209 Sdc1 NA 0.330139692 1.43E−12 Hspa5 1.02E−98 0.339769129 1.02E−98 Dap  5.49E−103 0.465257779  5.49E−103 Hsph1 1.92E−73 0.425977247 1.92E−73 Mrap NA 0.280974611 1.04E−10 Creld2 5.90E−44 0.362477611 5.90E−44 Cpox NA 0.294319953 2.98E−08 Ebp NA 0.252819864 3.69E−07 Fdps 7.67E−24 0.303232732 7.67E−24 Ugdh NA 0.260443532 4.68E−05 Tmpo NA 0.2573532 5.30E−05 Lss NA 0.294433908      0.00013007 Akr1d1 NA 0.258293189      0.00030931 Snord13 NA 0.408788625      0.00032705 Lsr NA 0.262580416      0.00577047 Tuba1c NA 0.302939755      0.00605691 Caprin1 2.84E−37 0.303020851 2.84E−37 Atl3 NA 0.255322039      0.02112341 Manf NA 0.282950631      0.02326868 Avpi1 NA 0.30186919      0.10146619 Krt8 NA 0.252276759      0.18282921 Sqle NA 1      0.27714068 Nucks1 NA 1      0.2710557 Lect2 NA 1 1.07E−19 Oat NA 1 4.82E−23 Tubb5 NA 1      0.31382452 Tubb4b NA 1      0.28149027 C4b 0 0.820022988 0 Vtn  8.96E−294 0.516935534  8.96E−294 Hc  2.31E−207 0.611232959  2.31E−207 Orm3  1.10E−191 0.517250103  1.10E−191 Serping1  3.54E−179 0.535830748  3.54E−179 Mpeg1  4.24E−174 0.541170007  4.24E−174 Cml2  7.24E−143 0.486040271  7.24E−143 Itih1  1.36E−141 0.496617676  1.36E−141 Comt  2.17E−123 0.384473508  2.17E−123 Calr  1.61E−116 0.391955529  1.61E−116 Scara5  2.62E−114 0.285535495  2.62E−114 Cfi  2.16E−113 0.390834066  2.16E−113 Mug2  3.40E−113 0.536577024  3.40E−113 H2-D1  1.14E−105 0.433183706  1.14E−105 Lpl  1.77E−105 0.355011922  1.77E−105 Col18a1  5.95E−103 0.459095159  5.95E−103 Wfdc17  1.32E−101 0.317329894  1.32E−101 Fetub 1.86E−98 0.425407474 1.86E−98 Serpinf2 7.60E−88 0.361403772 7.60E−88 H2-Q10 4.52E−87 0.250632773 4.52E−87 Aldh2 7.35E−82 0.296492218 7.35E−82 Cyp3a13 6.41E−81 0.420680082 6.41E−81 F5 1.06E−75 0.436709177 1.06E−75 Ldhd 1.04E−74 0.387086477 1.04E−74 Pcx 3.33E−72 0.367136085 3.33E−72 Fah 1.51E−71 0.325518495 1.51E−71 Abhd2 1.30E−66 0.267241512 1.30E−66 Ugt1a1 5.30E−66 0.370092558 5.30E−66 Cyr61 9.66E−64 0.302881921 9.66E−64 Pros1 3.01E−60 0.26812884 3.01E−60 Slc22a7 1.44E−59 0.307857498 1.44E−59 Ctss 2.68E−57 0.270183132 2.68E−57 P1xnb2 4.58E−57 0.381208682 4.58E−57 Gne 4.60E−57 0.355262513 4.60E−57 Abcb11 5.21E−57 0.351857633 5.21E−57 Cpn2 6.01E−57 0.349996687 6.01E−57 Lgals9 3.63E−55 0.327550674 3.63E−55 Hamp2 1.91E−54 0.337201585 1.91E−54 Psap 5.30E−54 0.318472244 5.30E−54 Mafb 1.15E−53 0.356246663 1.15E−53 Cd36 2.36E−53 0.291074527 2.36E−53 Pdia3 3.36E−53 0.276156858 3.36E−53 Habp2 3.50E−53 0.313462443 3.50E−53 Apon 2.92E−52 0.318989204 2.92E−52 Nbr1 4.73E−52 0.337157409 4.73E−52 Slc25a23 4.31E−51 0.332651576 4.31E−51 F9 1.74E−49 0.303980935 1.74E−49 Iigp1 4.95E−49 0.305889089 4.95E−49 Agt 4.95E−49 0.258205872 4.95E−49 Gns 9.33E−49 0.323226146 9.33E−49 Bsg 5.75E−48 0.273171859 5.75E−48 Scarb1 6.10E−48 0.32724782 6.10E−48 Sardh 2.96E−45 0.28626336 2.96E−45 Edem1 1.82E−44 0.301212478 1.82E−44 Abat 2.42E−44 0.305043176 2.42E−44 Dpyd 9.45E−44 0.315635393 9.45E−44 Myo18a 1.29E−42 0.253700048 1.29E−42 St6gal1 2.92E−42 0.295334926 2.92E−42 Tapbp 2.77E−41 0.265071778 2.77E−41 Ifih1 1.00E−40 0.264296168 1.00E−40 BC025446 4.46E−39 0.266911384 4.46E−39 Pcdh1 7.89E−39 0.265458741 7.89E−39 1300002K09Rik 1.78E−37 0.30148927 1.78E−37 Plec 2.04E−37 0.267122123 2.04E−37 Uba1 1.91E−36 0.281371963 1.91E−36 Kynu 2.94E−36 0.28095477 2.94E−36 Rxra 5.74E−36 0.264560061 5.74E−36 Tfr2 8.48E−36 0.268628506 8.48E−36 Ctnnd1 1.41E−35 0.252846161 1.41E−35 Fndc3a 7.28E−35 0.273177056 7.28E−35 Adh4 1.86E−34 0.282357284 1.86E−34 C130074G19Rik 3.22E−33 0.255729195 3.22E−33 Ptprf 4.49E−33 0.27768605 4.49E−33 Osbp19 1.06E−31 0.270713808 1.06E−31 Vwa8 1.52E−31 0.262040545 1.52E−31 Plcxd2 6.38E−31 0.266285463 6.38E−31 Serpina6 1.21E−30 0.269623074 1.21E−30 Mbl2 6.49E−30 0.268002193 5.49E−35 Pid1 2.30E−28 0.263310286 2.30E−28 Cmah 6.55E−28 0.251319774 6.55E−28 Aldh1b1 1.25E−25 0.360480753 1.25E−25 Rgn 2.71E−20 0.261094268 2.71E−20 Ifi27 5.38E−18 0.274586258 5.38E−18 Gulo 3.90E−10 0.282891961 3.90E−10 Slc1a2       0.006115724 0.262926395      0.00611572 Mup3 0 −1.423759103 0 Cyb5  2.13E−288 −0.751689441 0 mt-Rnr1 0 −0.872186844 0 mt-Rnr2 0 −0.967453486 0 Mup11 0 −1.769206667 0 mt-Nd2 0 −1.350784061 0 mt-Nd1 0 −1.543996447 0 mt-Nd5 0 −1.49645814 0 Gm13775  5.37E−288 −1.255657303 0 mt-Cytb 0 −1.554026854 0 mt-Co2  1.21E−274 −1.417328219 0 mt-Co1 0 −1.569950123 0 Mup5 0 −1.774609558 0 mt-Nd4 0 −1.953205815 0 Mup4 0 −1.945646142 0 Mup6 0 −2.645373468 0 Mup9 0 −2.520658851 0 Mup17 0 −2.514472885 0 Mup18 0 −2.617739049 0 Mup19 0 −3.632170505 0 mt-Co3  3.03E−229 −1.233961828  1.47E−287 Cyp2c29  3.62E−184 −1.027267705  2.76E−235 Mup16 0 −1.245137265 0 Cyp2b10  1.24E−168 −1.254972098  1.74E−217 Ankrd55  4.09E−185 −1.950942364  2.52E−247 Ugt2b5  5.77E−289 −0.716336886  5.77E−289 Apoe NA −0.615882949 0 Gsta3  3.08E−250 −0.796926805  3.08E−250 Cyp2c50 2.38E−78 −0.763912176  8.52E−186 Mup21 0 −1.637812283 0 Cyp2c54  1.42E−114 −0.712859584  1.75E−163 Akr1c6  3.18E−123 −0.501143524  6.85E−150 Apoc4  1.19E−182 −0.501759591  1.19E−182 mt-Atp6  3.13E−134 −0.914635453  7.98E−137 Mup15  5.96E−268 −1.364182598  5.96E−268 Cyp3a11 0 −0.803553063 0 Mgst1  2.20E−129 −0.36875402  2.50E−131 Cyp3a25 4.60E−99 −0.416456818  5.44E−129 Ces1d 0 −1.201503329 0 Mup13  6.29E−165 −0.875079323  6.29E−165 Cyp2c37  2.10E−130 −0.820386118  2.10E−130 Cyp2a5 1.93E−69 −0.938183249  8.06E−111 Serpina3c  4.68E−124 −0.595568461  4.68E−124 Adh1 NA −0.295980789  3.27E−106 Mup8  3.80E−123 −0.829956435  3.80E−123 Mup12 0 −1.228078411 0 Aldh1a1 NA −0.40245097  1.39E−102 Adck3 NA −0.569692886 4.38E−91 Ahcy  1.57E−115 −0.49011253  1.57E−115 Cox4i1  2.23E−168 −0.57523009  2.23E−168 Hsd3b7 NA −0.581642142 5.15E−93 Mup2  5.33E−115 −0.738721984  5.33E−115 Rsp14  3.76E−152 −0.607507888  3.76E−152 Ugt2b36 4.78E−87 −0.629671114  1.10E−145 Acaa1b 0 −0.855527427 0 Psen2 NA −0.419555606 1.69E−77 Cox6c  2.30E−132 −0.610222852  2.30E−132 Gm4076 7.57E−56 −0.345826319 7.98E−74 Uqcrq  2.42E−124 −0.485354968  2.42E−124 Igfbp2  3.60E−190 −0.717832911  3.60E−190 Rnf125 8.03E−30 −0.463320018 9.28E−70 mt-Nd6  2.74E−110 −0.685505467  2.74E−110 Rps2 3.26E−67 −0.474519664 4.24E−69 Hsd3b5 4.13E−58 −0.886463454  3.58E−129 Cyp1a2 8.09E−18 −0.481919967 3.86E−66 Rpl13a 2.24E−99 −0.480174283 2.24E−99 Rps27l  1.42E−139 −0.64582348  1.42E−139 Pon1 2.43E−57 −0.42825679 1.97E−64 Gm20594 1.33E−34 −0.573781187 4.48E−60 Mvd NA −0.327327327 2.22E−59 Sparcl1 2.01E−42 −0.253616986 3.78E−57 Malat1 4.45E−51 −0.652623643 6.64E−56 Cyp8b1  1.54E−120 −0.599290325  1.54E−120 Ugt2b34  1.12E−106 −0.500802828  1.12E−106 Hacl1 2.73E−36 −0.332899987 4.71E−52 Zfp683 3.13E−35 −0.421689112 1.10E−47 Oaf NA −0.333766768 3.11E−47 Cth 3.95E−48 −0.339209942 3.95E−48 Ndufb11 2.10E−70 −0.479044618 2.10E−70 Esd 5.03E−45 −0.381539462 1.94E−49 Mpc2 2.71E−68 −0.39520967 2.71E−68 Ubc NA −0.273242853 3.58E−41 Hebp1 3.96E−26 −0.313009472 1.26E−40 Gm5096 9.38E−37 −0.399548106 4.99E−39 Oaz1 1.67E−31 −0.426286153 1.27E−51 Cox7b  3.36E−144 −0.650085753  3.36E−144 Cyp2c55 2.21E−52 −0.347841415 2.21E−52 Inmt  1.56E−139 −0.679790467  1.56E−139 Cyp2e1 6.94E−06 −0.301497571 4.23E−36 Clpx 3.74E−21 −0.410840842 1.11E−53 Ndufb6 3.96E−85 −0.518384931 3.96E−85 Hist1h1c NA −0.331045753 5.78E−33 Elovl3  1.57E−229 −0.924845607  1.57E−229 Gm10250 1.11E−44 −0.336847064 1.11E−44 Arl4d NA −0.328520283 5.36E−30 Cml1 NA −0.47269345 5.55E−63 Hint2 3.41E−32 −0.373773572 2.60E−44 Aqp8 4.72E−23 −0.359788885 8.19E−45 Ndufa6 3.80E−59 −0.418444742 3.80E−59 Gm9843 9.49E−46 −0.396322103 9.49E−46 Atp5h 7.99E−68 −0.555498653 7.99E−68 Dcxr NA −0.271339616 1.59E−18 Cebpa NA −0.481611184 2.92E−66 Cyp4a10 9.75E−50 −0.698160085 2.61E−98 Sigmar1 NA −0.282364617 5.67E−17 Nr1i3 NA −0.317940692 1.11E−16 Ppp2r5a 3.25E−21 −0.315098874 3.37E−36 Hhex NA −0.283483187 9.95E−15 Rpl14 2.16E−37 −0.357060958 2.16E−37 Tprkb NA −0.254084951 1.31E−12 Cyp3a59 NA −0.263118105 3.34E−11 Rps18 1.19E−34 −0.415076007 1.19E−34 Ftl1 4.66E−11 −0.347806606 4.66E−11 Ubb NA −0.263773933      0.01387012 Mup1 1.78E−91 −0.882906956 1.78E−91 Mup7  8.04E−142 −0.847726732  8.04E−142 Gm24245 NA 1 3.33E−13 Mup14 8.52E−68 1 8.52E−68 Apoa2  1.04E−276 −0.615981195 0 Mup20 0 −1.237817166 0 Car3 0 −1.292191881 0 2810007J24Rik 7.72E−74 −1.093998287  2.63E−273 Tdo2  2.80E−102 −0.736504592  6.44E−267 Rbp4  4.52E−270 −0.580599925  4.52E−270 Fabp1 0 −0.826491833 0 Hsd11b1 6.95E−53 −0.998666341  3.95E−209 Ces3a NA −0.721008165  1.41E−206 Hmgcs2 NA −0.664269004  6.01E−206 Serpina1d NA −0.586852756  5.86E−199 Selenbp2 5.81E−73 −0.857199402  9.70E−194 Hrsp12 6.91E−87 −0.800669662  1.58E−182 Ces3b NA −0.819558687  6.86E−161 Cyp2d9 1.56E−76 −0.616676578  8.72E−151 Retsat  4.31E−216 −0.847260321  4.31E−216 Ugt2b1 1.59E−33 −0.722102286  5.69E−140 Serpina3k  2.79E−242 −0.298266533  2.79E−242 H2-K1 NA −0.596584494  1.74E−137 Cyp2f2 NA −0.887034648  5.25E−136 Pigr NA −0.661452  1.08E−134 Rdh7 NA −0.496910675  5.58E−132 Apoa1  6.60E−253 −0.411233725  6.60E−253 Apoh NA −0.417935459  3.98E−126 Aadac 6.31E−69 −0.747342823  6.76E−122 Ephx2 1.19E−91 −0.570800981  1.49E−121 Gpx1 NA −0.321984135  2.36E−120 Alb NA −0.427719117  2.56E−117 Otc NA −0.584972427  1.50E−116 Apoa5 NA −0.470514722  5.32E−149 Mug1 NA −0.497189268  3.61E−105 Acsl1 1.27E−85 −0.568030382  3.63E−104 Cyp4v3 NA −0.600614165  1.46E−101 Slco1a1 6.62E−92 −0.632477905  5.52E−101 Cfhr2 1.02E−63 −0.630617674 7.59E−98 B2m NA −0.430851295 2.11E−97 Khk NA −0.530150378 8.89E−91 Apoc1 NA −0.31073779 1.04E−90 Uox NA −0.480422343 1.42E−89 Rarres2 NA −0.492013911 1.76E−89 Serpina12 1.92E−45 −0.612367467 7.52E−89 Serpinc1 NA −0.333556351 1.38E−87 Ugt2a3 2.95E−72 −0.54739922 2.33E−87 Serpinf1 NA −0.506061854 3.06E−85 Ttr NA −0.286138394 3.87E−82 C8g NA −0.455638561 2.41E−80 Serpina1a 6.23E−81 −0.35536875 6.23E−81 Serpina1b NA −0.294480791 1.99E−74 Serpina1e 0 −0.72519719 0 Etnppl 1.59E−87 −0.566620392 1.59E−87 1500017E21Rik NA −0.517930222 1.93E−69 Atp5f1 1.10E−77 −0.460709866 1.10E−77 Ces1f  9.25E−112 −0.533638921  9.25E−112 Cyp4a12a NA −0.4760363 1.00E−65 Baat 1.48E−26 −0.445833101 1.01E−65 Fabp2 2.63E−76 −0.527186942 2.63E−76 Serpina1e NA −0.279835146 1.24E−63 Sod1  3.17E−216 −0.483374172  3.17E−216 Cdo1 NA −0.343333854 2.05E−63 Ech1  2.34E−114 −0.504022226  2.34E−114 Insig2 2.82E−25 −0.447606183 4.77E−62 Cox6a1 4.29E−41 −0.390617907 1.67E−61 Azgp1 NA −0.286918536 1.16E−60 Ces1c NA −0.274525359 5.85E−60 Pah NA −0.379853874 8.65E−60 Lipc NA −0.423055461 3.19E−59 Dio1 NA −0.469732353 9.15E−59 Aox3 NA −0.429460462 1.72E−66 Gstm1 1.73E−60 −0.448355325 1.73E−60 Slc27a5 NA −0.374625102 1.08E−57 Amy1 NA −0.441174 1.40E−57 Tmem205 NA −0.363762607 6.01E−57 Cyp2a12 NA −0.396631721 6.96E−57 Angptl3  2.66E−169 −0.529458826  2.66E−169 Cyp7b1 NA −0.438158056 1.37E−54 Hpd NA −0.317943335 2.00E−54 Ugp2 NA −0.394209561 6.59E−54 Ndufa4  4.13E−107 −0.512722876  4.13E−107 Nudt7 NA −0.566043759 9.48E−52 Slc10a1 4.19E−30 −0.395488081 8.15E−51 Scp2 NA −0.319519472  5.16E−159 Sco2 3.07E−16 −0.395951512 1.04E−49 Cyp2d10 9.23E−44 −0.325332653 3.76E−49 Chchd2  1.10E−119 −0.518624159  1.10E−119 Idh3b NA −0.360516268 4.19E−48 Bckdha NA −0.404702898 2.27E−47 Glo1 1.59E−34 −0.379233492 3.51E−47 Sdhb NA −0.357362255 2.51E−46 Cat NA −0.286016441 1.00E−45 Ces1e 9.70E−44 −0.375733204 2.06E−45 Cox5b 5.23E−43 −0.393691854 3.39E−45 Atp5g3 1.87E−78 −0.357248453 1.87E−78 Itm2b NA −0.261048932 4.20E−44 Etfdh NA −0.33708519 1.81E−43 Gsto1 NA −0.368935961 5.15E−43 Hsd3b3 NA −0.347460551 3.82E−42 Slc27a2 NA −0.305294922 2.23E−41 Hsd17b6 9.45E−46 −0.364685233 9.45E−46 Abcd3 NA −0.326838469 1.45E−40 Mdh1 NA −0.329025797 2.04E−40 Prdx4 1.74E−28 −0.378024564 3.39E−40 Hsd17b13 NA −0.376251609 1.14E−64 Proc NA −0.319776879 1.66E−39 Agxt NA −0.303827932 1.79E−39 Gls2 NA −0.353616749 1.09E−57 Ugt2b38 NA −0.250921219 1.20E−38 Ndufb9  1.07E−104 −0.483703094  1.07E−104 Rabac1 1.41E−19 −0.342063679 3.25E−38 Slc22a30 2.47E−15 −0.331870745 7.77E−38 Etfa NA −0.33793403 8.07E−38 Atp5j 7.16E−66 −0.415380683 7.16E−66 Uqcrfs1 NA −0.335765197 5.60E−37 Cyp27a1 NA −0.326228094 1.46E−36 Hal NA −0.304647432 3.02E−36 Sar1b 6.58E−68 −0.422088437 6.58E−68 Aldh6a1 NA −0.30870904 4.64E−36 Il1rap NA −0.302807638 1.94E−35 S100a1 NA −0.355544479 2.21E−35 Creg1  1.51E−125 −0.480113825  1.51E−125 1300017J02Rik NA −0.308343818 1.20E−34 Acat1 NA −0.290805818 1.81E−34 Pklr NA −0.283149611 4.04E−64 Dpys NA −0.313405671 8.84E−34 Aadat NA −0.325731706 9.13E−34 Cd81 NA −0.30883572 1.50E−33 Ndufc2 9.91E−31 −0.371342649 1.56E−33 Bphl NA −0.299478155 1.70E−33 Qdpr NA −0.316595182 1.80E−33 Gsta2 NA −0.284180552 4.56E−33 Acsm3 NA −0.280708005 5.27E−33 Cyp2d26 NA −0.270278674 2.04E−32 Cyp2c44 NA −0.312764543 2.09E−32 Hagh 4.45E−73 −0.398106396 4.45E−73 Ces2a  7.84E−141 −0.619093582  7.84E−141 Gas5 NA −0.298417518 6.31E−32 Uqcrb 6.07E−33 −0.359656695 6.07E−33 Gm4788 NA −0.297042332 1.49E−31 Slc2a2 NA −0.291267847 2.49E−31 Cela1 NA −0.252611197 1.03E−30 Hgd NA −0.273998205 2.46E−30 1110008F13Rik 1.42E−34 −0.327482854 1.42E−34 Csad  5.27E−267 −1.214863323  5.27E−267 Gabarapl1 NA −0.297156374 2.02E−29 Eci1 3.71E−30 −0.31335345 3.71E−30 Amdhd1 NA −0.272469871 8.10E−29 Uqcrh 5.89E−83 −0.483113531 5.89E−83 0610011F06Rik NA −0.28593883 3.51E−28 Ftcd NA −0.299187456 5.47E−28 Cyp4f14 NA −0.283565035 6.47E−28 Ttc39c NA −0.289612311 2.34E−27 Ndufv1 NA −0.256865664 2.43E−27 Pdhb NA −0.271619421 5.48E−27 Hsd17b11 NA −0.272884574 8.36E−27 Fcgrt NA −0.270945405 1.81E−26 Lyrm5 NA −0.251171881 3.08E−26 Bnip3 1.43E−18 −0.275946132 3.10E−26 Pygl NA −0.25405228 1.29E−25 C8b NA −0.251084368 1.50E−25 Atp5j2 3.23E−66 −0.409576712 3.23E−66 Fxyd1 NA −0.273422293 2.95E−25 Nit2 NA −0.255321274 6.79E−25 Sdha NA −0.286156431 7.96E−25 Pccb NA −0.266663529 8.00E−25 Park7 NA −0.270929309 9.02E−25 Cmbl NA −0.265365994 9.66E−25 Ces2e NA −0.272708804 8.71E−24 Cebpb 3.07E−10 −0.306330499 1.73E−23 Pbld1 NA −0.264627734 2.23E−23 Adipor2 NA −0.252551165 1.11E−22 Ephx1 2.60E−38 −0.332038055 2.60E−38 C6 NA −0.255102014 2.04E−21 Rn7sk NA −0.276399379 6.19E−14 Hint1  9.22E−101 −0.487016283  9.22E−101 Gstp1 4.28E−90 −0.671664785 4.28E−90 Gnmt 8.65E−84 −0.288175489 8.65E−84 Sc4mol 1.06E−80 −0.519568919 1.06E−80 Prdx1 2.27E−73 −0.353764247 2.27E−73 Rpl32 4.42E−73 −0.498592915 4.42E−73 Uqcr11 8.58E−61 −0.368070557 8.58E−61 Cox7a2 3.27E−59 −0.441101884 3.27E−59 Rps3 7.09E−57 −0.339903958 7.09E−57 Ndufb8 1.46E−55 −0.389897205 1.46E−55 Etfb 4.81E−54 −0.270014172 4.81E−54 Leap2 1.27E−50 −0.404792721 1.27E−50 Uqcr10 1.93E−47 −0.382321788 1.93E−47 Akr1c19 1.32E−46 −0.38253326 1.32E−46 Ddt 1.40E−46 −0.345838673 1.40E−46 Eef1b2 1.90E−45 −0.367328377 1.90E−45 Chchd10 5.22E−43 −0.28090926 5.22E−43 Rps24 6.91E−41 −0.386464837 6.91E−41 Acot1 2.65E−38 −0.299327096 2.65E−38 Cyp3a44 2.41E−34 −0.297417766 2.41E−34 Ndufb4 2.14E−33 −0.331687642 2.14E−33 Sdhd 2.47E−32 −0.302302961 2.47E−32 Rps5 1.17E−30 −0.25674004 1.17E−30 Ndufb2 1.21E−30 −0.336855533 1.21E−30 Blvrb 2.20E−30 −0.351075319 2.20E−30 Ndufs6 2.06E−29 −0.341035035 2.06E−29 Cnbp 2.46E−29 −0.286746587 2.46E−29 Cyp4a14 1.10E−28 −0.31778609 1.10E−28 Txn1 6.45E−28 −0.277353299 6.45E−28 Rpl36al 3.44E−26 −0.331844566 3.44E−26 Gadd45b 4.38E−25 −0.301158726 4.38E−25 G0s2 5.23E−25 −0.269113384 5.23E−25 Ssr4 7.71E−23 −0.283161199 7.71E−23 Minos1 8.00E−23 −0.308403636 8.00E−23 Ndufa2 9.67E−23 −0.308306345 9.67E−23 Tmem243 2.06E−22 −0.275109242 2.06E−22 Rps21 2.81E−22 −0.316866281 2.81E−22 Ndufa5 4.19E−22 −0.310280044 4.19E−22 Tubb2a 5.24E−22 −0.260491764 5.24E−22 Akr1c14 1.20E−21 −0.280169437 1.20E−21 Atp5o 2.25E−21 −0.268645357 2.25E−21 Psmb1 5.68E−21 −0.271574562 5.68E−21 Rps9 6.38E−21 −0.30861002 6.38E−21 Nme1 9.48E−21 −0.291609359 9.48E−21 Ndufb5 1.33E−20 −0.274484363 1.33E−20 Psma6 2.82E−20 −0.281709731 2.82E−20 Rplp1 6.89E−20 −0.274821325 6.89E−20 Fam162a 1.14E−19 −0.280519821 1.14E−19 4931406C07Rik 3.10E−19 −0.28178071 3.10E−19 Sc5d 3.96E−19 −0.274286355 3.96E−19 Timm13 1.44E−18 −0.266267617 1.44E−18 Ndufs4 2.26E−18 −0.299960018 2.26E−18 Selk 4.58E−18 −0.279248941 4.58E−18 Mrps18c 1.08E−17 −0.27427115 1.08E−17 Rpl13 3.52E−17 −0.314606263 7.45E−64 Rps8 2.52E−16 −0.279845708 2.52E−16 Rps15 3.43E−16 −0.324542895 3.43E−16 N1rp12 1.08E−15 −0.269307598 1.08E−15 Timm8b 2.42E−15 −0.25098905 2.42E−15 Dhrs4 5.96E−15 −0.268862728 5.96E−15 Rps10 3.85E−13 −0.252659935 3.85E−13 Rpl34 1.43E−12 −0.264586248 1.43E−12 Hspe1 3.13E−12 −0.257910168 3.13E−12 Usmg5 1.10E−10 −0.28365494 1.10E−10 Rpl26 1.36E−09 −0.264487941 1.36E−09 Rps19 5.15E−06 −0.25849266 5.15E−06

TABLE 8C Differentially expressed genes between treatment (APAP and PH). p_val avg_logFC pct.1 pct.2 p_val_adj cluster gene Hbb-bs 0 2.585900747 0.537 0.038 0 A6 Hbb-bs S100a9 0 1.342310796 0.399 0.005 0 A6 S100a9 Hmox1 0 1.339570861 0.558 0.026 0 A6 Hmox1 S100a8 0 1.127181553 0.353 0.002 0 A6 S100a8 Tnfrsf12a  4.64E−274 1.104985626 0.623 0.086  1.15E−269 A6 Tnfrsf12a Ccl6  8.63E−274 0.786807473 0.274 0.006  2.14E−269 A6 Ccl6 Hilpda  3.58E−254 0.780347895 0.403 0.028  8.90E−250 A6 Hilpda Mt2  4.30E−249 2.037681937 0.938 0.405  1.07E−244 A6 Mt2 Srgn  3.95E−244 0.928927613 0.284 0.01  9.80E−240 A6 Srgn Mt1  5.85E−244 2.320387581 0.981 0.602  1.45E−239 A6 Mt1 Srxn1  1.13E−243 1.864212779 0.821 0.239  2.80E−239 A6 Srxn1 Ppl  1.02E−233 0.861750145 0.47 0.049  2.54E−229 A6 Ppl Slc16a6  7.70E−208 0.913971966 0.47 0.058  1.91E−203 A6 Slc16a6 Gclc  1.87E−200 1.802382727 0.962 0.764  4.64E−196 A6 Gclc Cdkn1a  1.22E−180 1.251876494 0.702 0.195  3.04E−176 A6 Cdkn1a Plin2  1.48E−175 1.454290064 0.943 0.742  3.67E−171 A6 Plin2 Tubb6  1.52E−170 0.571531819 0.368 0.04  3.78E−166 A6 Tubb6 Actb  9.38E−169 1.051604326 0.979 0.893  2.33E−164 A6 Actb Clec4f  3.46E−163 1.124057361 0.339 0.034  8.59E−159 A6 Clec4f Chka  5.96E−156 1.403236367 0.716 0.24  1.48E−151 A6 Chka Txnrd1  7.87E−143 1.374708706 0.838 0.516  1.95E−138 A6 Txnrd1 Il1r1  5.63E−137 1.188669997 0.683 0.247  1.40E−132 A6 Il1r1 Krt18  3.50E−128 1.22726005 0.864 0.653  8.70E−124 A6 Krt18 Cidec  1.77E−123 0.30673991 0.253 0.024  4.40E−119 A6 Cidec Krt8  8.28E−122 1.273475842 0.826 0.564  2.06E−117 A6 Krt8 Klf6  8.56E−120 0.70668227 0.382 0.066  2.13E−115 A6 Klf6 Ets2  2.20E−109 0.68055198 0.415 0.087  5.47E−105 A6 Ets2 2010003K11Rik  3.63E−105 0.572900848 0.396 0.081  9.02E−101 A6 2010003K11Rik Tmsb4x  6.61E−105 0.791101995 0.332 0.055  1.64E−100 A6 Tmsb4x Cers6  1.33E−104 0.50707625 0.332 0.055  3.29E−100 A6 Cers6 Plscr1  2.32E−103 0.449697464 0.329 0.055 5.75E−99 A6 Plscr1 Rcan1 1.90E−94 0.700981932 0.425 0.105 4.72E−90 A6 Rcan1 Gm26924 2.05E−93 0.726922776 1 1 5.10E−89 A6 Gm26924 Myh9 2.39E−90 1.024834729 0.718 0.401 5.92E−86 A6 Myh9 Fgg 1.41E−82 0.47507836 0.986 0.995 3.50E−78 A6 Fgg Serpina3m 2.54E−82 0.793187331 0.85 0.772 6.30E−78 A6 Serpina3m C230081A13Rik 5.32E−82 0.418417199 0.279 0.049 1.32E−77 A6 C230081A13Rik Lrrc58 6.20E−82 0.939637116 0.711 0.429 1.54E−77 A6 Lrrc58 Fga 8.43E−81 0.50099721 0.986 0.997 2.09E−76 A6 Fga Apoa4 3.02E−80 1.166038714 0.721 0.434 7.51E−76 A6 Apoa4 Rell1 5.69E−79 0.579256897 0.375 0.095 1.41E−74 A6 Rell1 Bcl2l1 9.17E−79 0.741502458 0.501 0.182 2.28E−74 A6 Bcl2l1 Fgb 2.77E−76 0.477409638 0.995 1 6.88E−72 A6 Fgb Lars2 4.16E−75 0.814259119 1 0.995 1.03E−70 A6 Lars2 D10Wsu102e 3.45E−74 0.569827642 0.37 0.097 8.56E−70 A6 D10Wsu102e Gsta1 2.23E−70 0.408922304 0.32 0.073 5.53E−66 A6 Gsta1 Slc39a14 6.11E−70 0.916094428 0.678 0.428 1.52E−65 A6 Slc39a14 Mrap 9.06E−70 0.861482917 0.606 0.323 2.25E−65 A6 Mrap Gm15564 3.80E−66 0.786113662 0.983 0.967 9.43E−62 A6 Gm15564 1700017B05Rik 1.21E−62 0.327661725 0.255 0.052 3.00E−58 A6 1700017B05Rik Igfbp1 9.02E−61 1.089898094 0.792 0.702 2.24E−56 A6 Igfbp1 Sdc4 7.44E−59 0.567251857 0.909 0.892 1.85E−54 A6 Sdc4 Cldn14 1.21E−58 0.369504106 0.32 0.085 3.00E−54 A6 Cldn14 Alb 4.24E−58 0.374865074 1 1 1.05E−53 A6 Alb Sat1 3.50E−57 0.688728161 0.47 0.193 8.68E−53 A6 Sat1 Hnf4a 7.04E−57 0.696248102 0.835 0.805 1.75E−52 A6 Hnf4a Sqstm1 1.54E−56 0.699213054 0.859 0.828 3.83E−52 A6 Sqstm1 Fam134b 3.22E−56 0.815231577 0.678 0.482 8.00E−52 A6 Fam134b Nop58 2.76E−54 0.634296193 0.492 0.216 6.86E−50 A6 Nop58 Efhd2 4.11E−53 0.576644145 0.468 0.197 1.02E−48 A6 Efhd2 mmu-mir-6240 5.36E−53 1.031610172 0.413 0.149 1.33E−48 A6 mmu-mir-6240 Trp53inp1 9.22E−52 0.882913173 0.637 0.398 2.29E−47 A6 Trp53inp1 Epas1 5.89E−51 0.713771221 0.604 0.373 1.46E−46 A6 Epas1 Apob 8.74E−50 0.480248058 0.99 0.989 2.17E−45 A6 Apob Gcnt2 4.90E−49 0.503845296 0.372 0.131 1.22E−44 A6 Gcnt2 Eif1a 5.09E−49 0.722796481 0.599 0.373 1.26E−44 A6 Eif1a Insig2 1.13E−47 0.608089025 0.854 0.83 2.80E−43 A6 Insig2 Serpina3n 2.16E−47 0.664148633 0.747 0.658 5.38E−43 A6 Serpina3n Btg2 1.37E−46 0.766889798 0.549 0.303 3.40E−42 A6 Btg2 Agpat9 3.40E−46 0.304853757 0.277 0.077 8.45E−42 A6 Agpat9 Tra2a 1.23E−45 0.708051809 0.337 0.114 3.05E−41 A6 Tra2a Creb3l2 1.45E−44 0.397122997 0.329 0.11 3.61E−40 A6 Creb3l2 Stat3 1.26E−43 0.651998495 0.604 0.387 3.12E−39 A6 Stat3 Picalm 3.98E−43 0.676555334 0.647 0.452 9.89E−39 A6 Picalm Tubb2a 8.70E−43 0.785991182 0.618 0.443 2.16E−38 A6 Tubb2a Mat1a 9.42E−43 0.388871208 0.986 0.973 2.34E−38 A6 Mat1a Malat1 3.57E−42 0.985365756 0.871 0.75 8.87E−38 A6 Malat1 Cxadr 1.77E−41 0.656840533 0.606 0.408 4.40E−37 A6 Cxadr Myo1e 5.97E−41 0.578639718 0.475 0.237 1.48E−36 A6 Myo1e Bach1 8.93E−41 0.76858139 0.461 0.236 2.22E−36 A6 Bach1 Eif5 1.03E−40 0.480890827 0.816 0.786 2.56E−36 A6 Eif5 Tiparp 2.49E−40 0.524808466 0.346 0.131 6.18E−36 A6 Tiparp Cltc 7.70E−40 0.685231275 0.661 0.494 1.91E−35 A6 Cltc Ddx21 1.55E−39 0.655929312 0.535 0.316 3.84E−35 A6 Ddx21 Mdn1 2.43E−39 0.30793324 0.251 0.072 6.04E−35 A6 Mdn1 Heatr1 4.55E−39 0.381462092 0.291 0.095 1.13E−34 A6 Heatr1 H3f3b 4.97E−39 0.718378155 0.613 0.443 1.23E−34 A6 H3f3b Jmjd1c 3.17E−38 0.596320002 0.47 0.239 7.87E−34 A6 Jmjd1c Dot1l 4.16E−38 0.38526892 0.282 0.092 1.03E−33 A6 Dot1l Ctsl 6.53E−38 0.51275344 0.878 0.88 1.62E−33 A6 Ctsl Slc10a2 1.11E−37 0.270447751 0.255 0.077 2.75E−33 A6 Slc10a2 B4galt5 1.26E−37 0.423884611 0.332 0.126 3.12E−33 A6 B4galt5 Rock2 2.45E−37 0.555177626 0.425 0.199 6.08E−33 A6 Rock2 Dgkd 6.05E−37 0.358416905 0.282 0.094 1.50E−32 A6 Dgkd Lcn2 1.67E−36 0.387574636 0.301 0.106 4.14E−32 A6 Lcn2 Hspb8 1.95E−36 0.608924075 0.709 0.633 4.84E−32 A6 Hspb8 Ugdh 3.59E−36 0.608545157 0.721 0.647 8.92E−32 A6 Ugdh Ppan 9.70E−36 0.276685555 0.255 0.079 2.41E−31 A6 Ppan Xbp1 1.86E−35 0.569393474 0.692 0.611 4.62E−31 A6 Xbp1 Ddx5 2.16E−35 0.539662714 0.685 0.543 5.37E−31 A6 Ddx5 Tnfrsf1a 2.76E−35 0.568140336 0.508 0.305 6.86E−31 A6 Tnfrsf1a Tsr1 5.76E−35 0.339217996 0.341 0.135 1.43E−30 A6 Tsr1 Itih3 6.08E−35 0.404217046 0.907 0.913 1.51E−30 A6 Itih3 Ddx3x 6.10E−35 0.561165624 0.692 0.592 1.51E−30 A6 Ddx3x St3gal1 9.22E−35 0.516994152 0.473 0.262 2.29E−30 A6 St3gal1 Eaf1 1.20E−34 0.50717323 0.427 0.212 2.98E−30 A6 Eaf1 Hsd17b13 2.16E−34 0.480378763 0.864 0.761 5.37E−30 A6 Hsd17b13 Abca1 1.44E−33 0.65392515 0.604 0.438 3.58E−29 A6 Abca1 Hif1a 4.80E−33 0.487565104 0.427 0.213 1.19E−28 A6 Hif1a Tmem87b 1.08E−32 0.405411811 0.351 0.151 2.68E−28 A6 Tmem87b Fkbp5 1.20E−32 0.456737162 0.415 0.197 2.97E−28 A6 Fkbp5 C3 2.78E−32 0.278458208 0.993 0.993 6.90E−28 A6 C3 Spred1 3.89E−31 0.352013469 0.308 0.122 9.65E−27 A6 Spred1 Eef2 8.96E−31 0.405940418 0.9 0.899 2.23E−26 A6 Eef2 Gnl3 1.03E−30 0.49017644 0.501 0.3 2.56E−26 A6 Gnl3 Itih2 1.23E−30 0.392672893 0.893 0.914 3.06E−26 A6 Itih2 Stk40 4.64E−30 0.493002444 0.382 0.184 1.15E−25 A6 Stk40 Tjp2 4.42E−29 0.396131523 0.332 0.147 1.10E−24 A6 Tjp2 Lyst 1.82E−28 0.371733248 0.31 0.127 4.52E−24 A6 Lyst Errfi1 2.21E−28 0.342085301 0.943 0.931 5.50E−24 A6 Errfi1 Chic2 3.18E−28 0.396396418 0.37 0.181 7.89E−24 A6 Chic2 Rad54l2 3.33E−28 0.364207232 0.325 0.139 8.26E−24 A6 Rad54l2 Mfsd2a 4.59E−28 0.461048631 0.465 0.263 1.14E−23 A6 Mfsd2a Sdad1 1.02E−27 0.296939107 0.289 0.115 2.54E−23 A6 Sdad1 Bcl3 2.52E−27 0.274060002 0.277 0.109 6.26E−23 A6 Bcl3 Neat1 3.08E−27 0.655410081 0.31 0.135 7.66E−23 A6 Neat1 Asl 4.46E−27 0.41345396 0.826 0.822 1.11E−22 A6 Asl Tcerg1 5.22E−27 0.346807528 0.305 0.132 1.30E−22 A6 Tcerg1 Tacc2 5.92E−27 0.312763874 0.289 0.116 1.47E−22 A6 Tacc2 Gpt2 9.88E−27 0.469474425 0.764 0.767 2.45E−22 A6 Gpt2 Abhd2 2.12E−26 0.414892908 0.37 0.181 5.25E−22 A6 Abhd2 Cyp4a14 2.69E−26 0.333371288 0.776 0.554 6.69E−22 A6 Cyp4a14 Ptpn1 4.30E−26 0.386530538 0.353 0.165 1.07E−21 A6 Ptpn1 Fndc3b 9.70E−26 0.349610838 0.315 0.14 2.41E−21 A6 Fndc3b Tsku 3.63E−25 0.333177586 0.327 0.148 9.01E−21 A6 Tsku Nolc1 6.52E−25 0.444492735 0.363 0.183 1.62E−20 A6 Nolc1 Jak1 1.07E−24 0.543711884 0.554 0.415 2.67E−20 A6 Jak1 Tsc22d2 2.31E−24 0.362913692 0.353 0.175 5.73E−20 A6 Tsc22d2 Btg1 2.53E−24 0.398422802 0.356 0.177 6.29E−20 A6 Btg1 Son 2.57E−24 0.455496144 0.601 0.439 6.39E−20 A6 Son Lpin2 3.86E−24 0.516521417 0.745 0.687 9.59E−20 A6 Lpin2 Iigp1 5.96E−24 0.643134023 0.78 0.805 1.48E−19 A6 Iigp1 St3gal5 6.19E−24 0.435791231 0.706 0.581 1.54E−19 A6 St3gal5 n-R5-8s1 1.02E−23 0.400510777 0.308 0.135 2.53E−19 A6 n-R5-8s1 Eif4g2 1.15E−23 0.412563051 0.757 0.748 2.86E−19 A6 Eif4g2 Gjb2 2.31E−23 0.503822785 0.678 0.644 5.73E−19 A6 Gjb2 Dusp16 1.08E−22 0.427321245 0.372 0.203 2.68E−18 A6 Dusp16 Pfkfb2 1.30E−22 0.269394194 0.26 0.108 3.23E−18 A6 Pfkfb2 Tars 1.56E−22 0.471782286 0.666 0.587 3.87E−18 A6 Tars Rora 2.50E−22 0.540962509 0.549 0.433 6.22E−18 A6 Rora Plec 3.98E−22 0.418829547 0.422 0.244 9.88E−18 A6 Plec Gm26917 6.93E−22 0.423906459 0.382 0.204 1.72E−17 A6 Gm26917 Mpeg1 1.75E−21 0.466789938 0.263 0.113 4.34E−17 A6 Mpeg1 Mat2a 3.17E−21 0.475830508 0.487 0.332 7.86E−17 A6 Mat2a Gtpbp4 3.37E−21 0.462339077 0.477 0.317 8.37E−17 A6 Gtpbp4 Ranbp2 4.52E−21 0.507425104 0.566 0.435 1.12E−16 A6 Ranbp2 Map2k3 6.02E−21 0.414970013 0.427 0.262 1.50E−16 A6 Map2k3 Mcl1 6.44E−21 0.524900127 0.573 0.434 1.60E−16 A6 Mcl1 Slc20a1 1.39E−20 0.326037889 0.284 0.131 3.44E−16 A6 Slc20a1 Cars 1.86E−20 0.306735271 0.329 0.166 4.61E−16 A6 Cars Ywhag 3.03E−20 0.513182681 0.518 0.392 7.52E−16 A6 Ywhag Retsat 4.73E−20 0.291831196 0.845 0.85 1.18E−15 A6 Retsat Etf1 4.99E−20 0.452556434 0.606 0.499 1.24E−15 A6 Etf1 Epb4.1 6.09E−20 0.467770072 0.537 0.403 1.51E−15 A6 Epb4.1 Myl12a 8.41E−20 0.402881373 0.461 0.306 2.09E−15 A6 Myl12a Dusp6 3.85E−19 0.508677973 0.482 0.335 9.57E−15 A6 Dusp6 Gm20594 7.21E−19 0.440502144 0.442 0.259 1.79E−14 A6 Gm20594 Lrg1 7.52E−19 0.332404269 0.783 0.797 1.87E−14 A6 Lrg1 Dkc1 8.07E−19 0.30544641 0.315 0.162 2.00E−14 A6 Dkc1 App 1.30E−18 0.338059459 0.315 0.162 3.23E−14 A6 App Rnd3 1.41E−18 0.326746608 0.284 0.14 3.50E−14 A6 Rnd3 Ncl 1.56E−18 0.388188482 0.69 0.639 3.88E−14 A6 Ncl Tatdn2 1.76E−18 0.324760981 0.334 0.176 4.36E−14 A6 Tatdn2 Fam107b 2.12E−18 0.416215114 0.449 0.307 5.26E−14 A6 Fam107b Tns1 3.23E−18 0.400122808 0.403 0.254 8.02E−14 A6 Tns1 Phc2 3.78E−18 0.298986746 0.284 0.141 9.39E−14 A6 Phc2 Tbc1d15 3.97E−18 0.432216558 0.461 0.319 9.86E−14 A6 Tbc1d15 Dst 3.98E−18 0.447341116 0.43 0.276 9.87E−14 A6 Dst Lmo4 4.29E−18 0.296248817 0.308 0.162 1.06E−13 A6 Lmo4 Egr1 5.65E−18 0.537039177 0.589 0.481 1.40E−13 A6 Egr1 Hnrnpdl 8.07E−18 0.399328599 0.406 0.254 2.00E−13 A6 Hnrnpdl Aff4 1.70E−17 0.536338474 0.537 0.423 4.23E−13 A6 Aff4 Gn12 1.83E−17 0.358031458 0.384 0.235 4.55E−13 A6 Gn12 Lrrfip1 2.21E−17 0.410825691 0.37 0.221 5.49E−13 A6 Lrrfip1 Aass 2.35E−17 0.40708364 0.747 0.763 5.83E−13 A6 Aass Kif5b 8.07E−17 0.452231438 0.494 0.379 2.00E−12 A6 Kif5b Wbp1l 1.01E−16 0.389703337 0.697 0.683 2.52E−12 A6 Wbp1l Stom 1.12E−16 0.299958852 0.329 0.184 2.77E−12 A6 Stom Arhgef12 1.63E−16 0.485612023 0.578 0.494 4.05E−12 A6 Arhgef12 Pxk 4.69E−16 0.265227811 0.303 0.161 1.16E−11 A6 Pxk Prrc2c 6.21E−16 0.390594415 0.415 0.266 1.54E−11 A6 Prrc2c Sds 6.91E−16 0.351547188 0.73 0.632 1.72E−11 A6 Sds Mybbp1a 7.16E−16 0.401802664 0.396 0.263 1.78E−11 A6 Mybbp1a Wdr43 8.36E−16 0.308292044 0.353 0.208 2.08E−11 A6 Wdr43 Mmp14 9.37E−16 0.257143847 0.253 0.125 2.33E−11 A6 Mmp14 Ptpn2 9.68E−16 0.270962207 0.255 0.124 2.40E−11 A6 Ptpn2 Mak16 1.01E−15 0.28973233 0.267 0.134 2.51E−11 A6 Mak16 Plk3 1.73E−15 0.415826723 0.413 0.269 4.29E−11 A6 Plk3 Tm4sf4 2.46E−15 0.400558068 0.484 0.363 6.11E−11 A6 Tm4sf4 Cyp39a1 4.02E−15 0.299582361 0.305 0.171 9.99E−11 A6 Cyp39a1 Nedd4l 4.88E−15 0.263544573 0.332 0.189 1.21E−10 A6 Nedd4l Ptpn12 6.24E−15 0.309327486 0.263 0.135 1.55E−10 A6 Ptpn12 Map3k5 6.60E−15 0.313064805 0.346 0.206 1.64E−10 A6 Map3k5 Nars 7.95E−15 0.368685334 0.606 0.539 1.97E−10 A6 Nars Ptp4a1 9.30E−15 0.251709471 0.334 0.192 2.31E−10 A6 Ptp4a1 Gm24245 1.17E−14 0.498425809 0.422 0.269 2.89E−10 A6 Gm24245 Ifrd1 1.21E−14 0.476476582 0.365 0.226 3.00E−10 A6 Ifrd1 AA474408 1.38E−14 0.266419343 0.274 0.142 3.42E−10 A6 AA474408 Zyx 2.09E−14 0.279857668 0.263 0.137 5.20E−10 A6 Zyx Smg1 2.32E−14 0.304468325 0.265 0.141 5.76E−10 A6 Smg1 Man2a1 3.27E−14 0.343929917 0.671 0.659 8.13E−10 A6 Man2a1 Lrrfip2 3.29E−14 0.356490426 0.384 0.247 8.16E−10 A6 Lrrfip2 Ppp1r12a 3.38E−14 0.325164021 0.317 0.182 8.39E−10 A6 Ppp1r12a Chd1 4.71E−14 0.314128487 0.377 0.243 1.17E−09 A6 Chd1 Lpgat1 5.37E−14 0.443498962 0.618 0.593 1.33E−09 A6 Lpgat1 Palld 6.63E−14 0.3083699 0.353 0.218 1.65E−09 A6 Palld H2-D1 6.78E−14 0.298627546 0.766 0.781 1.68E−09 A6 H2-D1 Grn 7.22E−14 0.373811784 0.582 0.499 1.79E−09 A6 Grn Fus 1.11E−13 0.338818431 0.394 0.267 2.76E−09 A6 Fus Litaf 1.26E−13 0.351166994 0.451 0.34 3.13E−09 A6 Litaf Mki67ip 1.50E−13 0.312167827 0.344 0.212 3.73E−09 A6 Mki67ip Lcp1 2.39E−13 0.464895097 0.492 0.365 5.94E−09 A6 Lcp1 mt-Rnr1 2.60E−13 0.390086647 1 1 6.45E−09 A6 mt-Rnr1 Ctsb 2.79E−13 0.469114925 0.804 0.82 6.94E−09 A6 Ctsb Sptbn1 3.21E−13 0.376219831 0.439 0.325 7.98E−09 A6 Sptbn1 Sfpq 5.31E−13 0.34484544 0.406 0.277 1.32E−08 A6 Sfpq Tgm2 5.71E−13 0.362144298 0.446 0.314 1.42E−08 A6 Tgm2 Eif4g1 1.45E−12 0.314414152 0.723 0.719 3.60E−08 A6 Eif4g1 Fn1 2.32E−12 0.28519688 0.847 0.866 5.76E−08 A6 Fn1 Purb 2.57E−12 0.310815573 0.341 0.219 6.37E−08 A6 Purb Phlda1 2.84E−12 0.472335823 0.494 0.429 7.05E−08 A6 Phlda1 Atp2a2 3.95E−12 0.364622996 0.616 0.575 9.81E−08 A6 Atp2a2 Etnppl 6.99E−12 0.30440999 0.706 0.62 1.74E−07 A6 Etnppl Akap13 7.44E−12 0.443592591 0.406 0.282 1.85E−07 A6 Akap13 Wdr26 1.07E−11 0.372353239 0.549 0.472 2.66E−07 A6 Wdr26 Huwe1 1.08E−11 0.333579982 0.492 0.38 2.69E−07 A6 Huwe1 Cald1 1.16E−11 0.293474512 0.766 0.795 2.89E−07 A6 Cald1 Ankrd11 1.30E−11 0.371489147 0.389 0.263 3.24E−07 A6 Ankrd11 Mbnl1 2.38E−11 0.34826585 0.492 0.394 5.91E−07 A6 Mbnl1 Mug2 2.45E−11 0.277303056 0.776 0.77 6.09E−07 A6 Mug2 Rn7sk 2.61E−11 0.277601787 0.339 0.212 6.48E−07 A6 Rn7sk Anxa5 2.84E−11 0.357988662 0.391 0.278 7.05E−07 A6 Anxa5 Metap2 4.08E−11 0.327962496 0.453 0.353 1.01E−06 A6 Metap2 Shb 4.85E−11 0.283085429 0.382 0.264 1.20E−06 A6 Shb Gsr 4.90E−11 0.392388862 0.453 0.346 1.22E−06 A6 Gsr Gsk3b 5.45E−11 0.35404888 0.384 0.272 1.35E−06 A6 Gsk3b Kdelr2 5.86E−11 0.36902044 0.484 0.413 1.45E−06 A6 Kdelr2 Tjp1 1.36E−10 0.252895758 0.251 0.142 3.37E−06 A6 Tjp1 Sf1 2.46E−10 0.277710053 0.351 0.233 6.11E−06 A6 Sf1 Dhx9 3.77E−10 0.305614472 0.427 0.319 9.37E−06 A6 Dhx9 Smap2 4.08E−10 0.317056211 0.363 0.246 1.01E−05 A6 Smap2 Chmp4b 4.61E−10 0.293914095 0.442 0.344 1.14E−05 A6 Chmp4b Cxcl1 5.14E−10 0.309204773 0.444 0.334 1.28E−05 A6 Cxcl1 Snx10 5.28E−10 0.264074664 0.341 0.232 1.31E−05 A6 Snx10 Pacsin2 5.77E−10 0.342565625 0.37 0.264 1.43E−05 A6 Pacsin2 Cast 7.34E−10 0.341920461 0.399 0.293 1.82E−05 A6 Cast Akap11 7.52E−10 0.297231801 0.351 0.24 1.87E−05 A6 Akap11 Srsf11 7.58E−10 0.354232945 0.418 0.313 1.88E−05 A6 Srsf11 Reep3 9.04E−10 0.335070143 0.535 0.502 2.24E−05 A6 Reep3 mmu-mir-6236 1.28E−09 0.420467035 0.831 0.853 3.19E−05 A6 mmu-mir-6236 Atf4 2.02E−09 0.286714844 0.58 0.505 5.02E−05 A6 Atf4 Clic4 2.32E−09 0.2810953 0.368 0.265 5.77E−05 A6 Clic4 Ubr4 2.43E−09 0.291606896 0.411 0.302 6.03E−05 A6 Ubr4 Por 2.58E−09 0.268724257 0.704 0.721 6.42E−05 A6 Por Bptf 2.63E−09 0.281824549 0.332 0.222 6.53E−05 A6 Bptf Zbtb20 2.91E−09 0.378048195 0.566 0.519 7.23E−05 A6 Zbtb20 Dync1h1 3.26E−09 0.341961739 0.379 0.275 8.10E−05 A6 Dync1h1 Rlim 3.27E−09 0.275758769 0.305 0.199 8.12E−05 A6 Rlim Birc6 4.85E−09 0.292199154 0.446 0.34 0.000120422 A6 Birc6 Atp1b1 5.41E−09 0.313967935 0.391 0.294 0.000134226 A6 Atp1b1 Slc25a47 6.75E−09 0.288429921 0.869 0.931 0.000167694 A6 Slc25a47 Slc25a51 7.23E−09 0.253289156 0.308 0.203 0.000179545 A6 Slc25a51 Jhdm1d 7.29E−09 0.254152235 0.279 0.177 0.000181067 A6 Jhdm1d Steap4 9.00E−09 0.36530445 0.37 0.275 0.000223544 A6 Steap4 Mapkapk2 9.71E−09 0.30529864 0.396 0.294 0.000241093 A6 Mapkapk2 Gtf2a2 1.09E−08 0.265404263 0.379 0.28 0.000271551 A6 Gtf2a2 Slc4a4 1.12E−08 0.295268979 0.513 0.439 0.000278519 A6 Slc4a4 Tbl1xr1 1.79E−08 0.255321469 0.341 0.246 0.000443552 A6 Tbl1xr1 Sbno1 1.89E−08 0.296206562 0.394 0.301 0.000469821 A6 Sbno1 Nrp1 1.98E−08 0.320317373 0.391 0.295 0.00049277 A6 Nrp1 Tpr 2.01E−08 0.352440039 0.501 0.429 0.000499279 A6 Tpr Kif21a 2.01E−08 0.333362777 0.461 0.377 0.000500319 A6 Kif21a Mdm2 2.06E−08 0.275809807 0.305 0.204 0.000510843 A6 Mdm2 Ddx6 2.13E−08 0.347331371 0.527 0.46 0.000529761 A6 Ddx6 Rbm25 2.41E−08 0.365024904 0.461 0.369 0.000598306 A6 Rbm25 Uhrf1bp1l 2.44E−08 0.319283953 0.399 0.306 0.000606861 A6 Uhrf1bp1l Cep85 3.36E−08 0.270833691 0.313 0.215 0.00083347 A6 Cep85 Hmgcr 3.52E−08 0.344898662 0.425 0.343 0.000873878 A6 Hmgcr Saa2 4.22E−08 0.38920839 0.315 0.221 0.001047242 A6 Saa2 Tnks2 5.05E−08 0.267384994 0.358 0.265 0.001254373 A6 Tnks2 Net1 5.81E−08 0.320110712 0.408 0.324 0.001441888 A6 Net1 Rangap1 6.81E−08 0.271467828 0.387 0.298 0.001690824 A6 Rangap1 Atp13a3 8.04E−08 0.298039121 0.532 0.494 0.001997402 A6 Atp13a3 Tmed5 9.87E−08 0.262840646 0.594 0.587 0.002451811 A6 Tmed5 Atp2b1 1.14E−07 0.289377372 0.334 0.239 0.002830088 A6 Atp2b1 Ell2 1.24E−07 0.307296281 0.535 0.508 0.003081707 A6 Ell2 Eif4a1 1.50E−07 0.260785213 0.418 0.331 0.003715312 A6 Eif4a1 Macf1 1.58E−07 0.347805477 0.377 0.287 0.003914779 A6 Macf1 Srrm2 1.83E−07 0.286594156 0.456 0.372 0.004531922 A6 Srrm2 Brd2 1.86E−07 0.459822776 0.542 0.493 0.004608791 A6 Brd2 Ipo7 1.95E−07 0.267191431 0.334 0.241 0.004846455 A6 Ipo7 Cap1 2.19E−07 0.285316115 0.356 0.261 0.005437156 A6 Cap1 Lrrc59 2.71E−07 0.30237878 0.422 0.354 0.006720029 A6 Lrrc59 Scaf11 3.09E−07 0.287560725 0.449 0.382 0.007680311 A6 Scaf11 Phf20l1 3.47E−07 0.265681682 0.372 0.282 0.008627157 A6 Phf20l1 Hipk3 3.52E−07 0.260488512 0.396 0.309 0.008752398 A6 Hipk3 Prpf19 3.65E−07 0.256584518 0.432 0.356 0.009072104 A6 Prpf19 Actr3 4.09E−07 0.263828451 0.36 0.273 0.0101555 A6 Actr3 Gfra1 5.26E−07 0.275822348 0.599 0.583 0.013059775 A6 Gfra1 Dnajc5 5.58E−07 0.263545549 0.372 0.294 0.013867302 A6 Dnajc5 Gm5424 7.53E−07 0.264697117 0.411 0.325 0.018693371 A6 Gm5424 Ppip5k2 7.82E−07 0.300238752 0.344 0.254 0.019412805 A6 Ppip5k2 Yap1 8.00E−07 0.261525975 0.375 0.288 0.019872963 A6 Yap1 mt-Co1 1.20E−06 0.351015168 0.998 0.988 0.029744292 A6 mt-Co1 Mgea5 1.25E−06 0.290424441 0.413 0.333 0.031079611 A6 Mgea5 Kpna1 1.55E−06 0.255454573 0.363 0.286 0.038470274 A6 Kpna1 Atf6 1.79E−06 0.292221667 0.432 0.365 0.04443216 A6 Atf6 Ivns1abp 1.94E−06 0.275508294 0.446 0.398 0.048239404 A6 Ivns1abp Dnaja2 2.46E−06 0.299312472 0.516 0.482 0.06120923 A6 Dnaja2 Ctsc 2.59E−06 0.257615328 0.403 0.321 0.064323031 A6 Ctsc Kdm5a 2.84E−06 0.310177967 0.308 0.221 0.070537642 A6 Kdm5a Abce1 2.87E−06 0.250233228 0.437 0.365 0.071298568 A6 Abce1 Rsl1d1 3.31E−06 0.274880418 0.47 0.423 0.08207937 A6 Rsl1d1 Eprs 4.18E−06 0.297658536 0.566 0.558 0.10382179 A6 Eprs Hnrnpu 5.29E−06 0.250578107 0.625 0.651 0.131375216 A6 Hnrnpu H6pd 5.50E−06 0.256150539 0.623 0.652 0.136642791 A6 H6pd mt-Nd5 6.52E−06 0.341125985 0.983 0.969 0.161943697 A6 mt-Nd5 Rnf169 7.00E−06 0.296323635 0.315 0.235 0.173720819 A6 Rnf169 Rap1b 7.33E−06 0.284122894 0.406 0.335 0.181944357 A6 Rap1b Chuk 8.66E−06 0.295478719 0.523 0.495 0.214923523 A6 Chuk Sf3b1 9.81E−06 0.250611588 0.508 0.475 0.243582219 A6 Sf3b1 Serinc3 1.22E−05 0.2811911 0.525 0.498 0.303917936 A6 Serinc3 Pi4k2a 1.25E−05 0.327022483 0.425 0.381 0.310307299 A6 Pi4k2a Alcam 1.35E−05 0.264774262 0.396 0.329 0.33420498 A6 Alcam Gadd45a 1.39E−05 0.282094324 0.251 0.178 0.344761555 A6 Gadd45a Diap1 1.79E−05 0.281572774 0.382 0.306 0.444812392 A6 Diap1 Ddx3y 3.35E−05 0.277824135 0.47 0.43 0.83189176 A6 Ddx3y Eif4b 3.52E−05 0.278878236 0.542 0.521 0.873426916 A6 Eif4b Nploc4 5.58E−05 0.251530839 0.351 0.28 1 A6 Nploc4 Nucks1 7.26E−05 0.260380087 0.532 0.517 1 A6 Nucks1 Tab2 7.82E−05 0.293074476 0.425 0.374 1 A6 Tab2 Slc35d1 8.85E−05 0.253786261 0.489 0.496 1 A6 Slc35d1 Abcc2 8.98E−05 0.260028664 0.632 0.654 1 A6 Abcc2 Atp1a1 9.45E−05 0.291312422 0.53 0.538 1 A6 Atp1a1 Slc40a1 0.00029608 0.349948116 0.456 0.417 1 A6 Slc40a1 Zfp106 0.000319641 0.270672764 0.391 0.333 1 A6 Zfp106 Ier2 0.000367025 0.250748851 0.551 0.517 1 A6 Ier2 Trip11 0.000589236 0.287017056 0.341 0.284 1 A6 Trip11 Srsf5 0.000641609 0.253489779 0.387 0.34 1 A6 Srsf5 Spag9 0.001729185 0.25323185 0.415 0.373 1 A6 Spag9 Tln1 0.00250885 0.293695038 0.31 0.259 1 A6 Tln1 Riok3 0.003018499 0.258919292 0.43 0.406 1 A6 Riok3 mt-Nd6 0.003486244 0.290617021 0.527 0.502 1 A6 mt-Nd6 Gm269241 0 1.253161452 1 1 0 A24 Gm26924 n-R5-8s11 0 1.150811396 0.522 0.075 0 A24 n-R5-8s1 Grip2 0 0.877370568 0.475 0.003 0 A24 Grip2 Fga1 0 0.762040686 0.998 0.996 0 A24 Fga Fgb1 0 0.681029638 1 0.999 0 A24 Fgb Fgg1 0 0.633396491 0.999 0.993 0 A24 Fgg Lars21  1.08E−286 1.493131216 0.998 0.995  2.69E−282 A24 Lars2 Sephs21  1.58E−286 0.853566054 0.949 0.785  3.91E−282 A24 Sephs2 Fgl1  5.87E−275 0.874063594 0.938 0.799  1.46E−270 A24 Fgl1 Gm24601  4.02E−274 0.932441655 0.404 0.047  9.99E−270 A24 Gm24601 Gm155641  3.89E−272 1.555434308 0.982 0.965  9.67E−268 A24 Gm15564 Calr1  5.92E−193 0.611584258 0.952 0.882  1.47E−188 A24 Calr Pdia31  3.00E−171 0.642410377 0.895 0.805  7.45E−167 A24 Pdia3 Hyou1  1.92E−169 0.843594109 0.717 0.423  4.77E−165 A24 Hyou1 Saa21  1.56E−157 1.00910228 0.52 0.172  3.88E−153 A24 Saa2 Hsp90b11  2.63E−155 0.545125445 0.954 0.948  6.53E−151 A24 Hsp90b1 Sepp1  5.04E−153 0.326034322 1 1  1.25E−148 A24 Sepp1 Hspa5  1.66E−152 0.489951106 0.974 0.954  4.12E−148 A24 Hspa5 Orm1  6.97E−135 0.466115424 0.963 0.942  1.73E−130 A24 Orm1 Itih4  2.79E−129 0.46889806 0.974 0.956  6.93E−125 A24 Itih4 Egfr  2.69E−128 0.62342268 0.882 0.802  6.67E−124 A24 Egfr Glud1  1.70E−115 0.42115272 0.958 0.921  4.22E−111 A24 Glud1 Hp  2.71E−113 0.364354354 0.998 0.999  6.73E−109 A24 Hp Mup71  1.68E−111 0.268129829 0.985 0.965  4.16E−107 A24 Mup7 Serpina101  2.00E−108 0.570729192 0.813 0.667  4.97E−104 A24 Serpina10 Rnase41  2.35E−108 0.554006694 0.963 0.898  5.83E−104 A24 Rnase4 Scd11  2.78E−104 0.558572468 0.98 0.925  6.90E−100 A24 Scd1 Eef1a1  2.17E−101 0.456135198 0.919 0.858 5.38E−97 A24 Eef1a1 Saa1  2.48E−100 0.781172408 0.792 0.549 6.16E−96 A24 Saa1 C8b1 1.53E−99 0.440139433 0.898 0.871 3.79E−95 A24 C8b Hdlbp 2.71E−98 0.527847395 0.853 0.753 6.72E−94 A24 Hdlbp Cyp2c701 7.78E−90 0.479527584 0.89 0.823 1.93E−85 A24 Cyp2c70 P4hb1 2.74E−89 0.332542787 0.973 0.945 6.82E−85 A24 P4hb Apcs 5.47E−89 0.605911685 0.738 0.556 1.36E−84 A24 Apcs Creld2 5.15E−88 0.594060178 0.583 0.352 1.28E−83 A24 Creld2 C91 2.56E−84 0.375762746 0.952 0.926 6.35E−80 A24 C9 Orm2 5.62E−84 0.304652907 0.285 0.081 1.40E−79 A24 Orm2 Ssr3 1.77E−83 0.486117928 0.765 0.642 4.40E−79 A24 Ssr3 Pzp 4.35E−83 0.354307454 0.984 0.988 1.08E−78 A24 Pzp C31 2.09E−82 0.323813995 0.996 0.993 5.18E−78 A24 C3 Arrdc31 1.19E−81 0.498916524 0.52 0.272 2.97E−77 A24 Arrdc3 Saa41 1.26E−81 0.476275836 0.823 0.734 3.13E−77 A24 Saa4 Fn11 3.93E−80 0.553626994 0.905 0.858 9.76E−76 A24 Fn1 Cfh 3.78E−79 0.454722845 0.921 0.904 9.38E−75 A24 Cfh Cat 3.96E−78 0.285637918 0.978 0.977 9.84E−74 A24 Cat Actb1 4.53E−78 0.322827073 0.919 0.895 1.12E−73 A24 Actb Pdia41 2.83E−76 0.520868525 0.733 0.616 7.02E−72 A24 Pdia4 Sc5d1 4.88E−76 0.398810219 0.879 0.797 1.21E−71 A24 Sc5d Steap41 5.67E−76 0.466342007 0.481 0.243 1.41E−71 A24 Steap4 C8a 1.03E−72 0.424002753 0.902 0.877 2.55E−68 A24 C8a Pgrmc1 1.30E−70 0.307565593 0.953 0.947 3.22E−66 A24 Pgrmc1 Itih31 3.45E−70 0.393234979 0.931 0.909 8.58E−66 A24 Itih3 Nudt71 3.41E−69 0.34725512 0.884 0.74 8.47E−65 A24 Nudt7 Hc 5.21E−67 0.388992856 0.905 0.904 1.29E−62 A24 Hc Tram1 1.87E−66 0.42942297 0.7 0.545 4.63E−62 A24 Tram1 Myh91 1.24E−65 0.491944623 0.595 0.388 3.08E−61 A24 Myh9 Mup121 1.65E−65 0.453275054 0.799 0.759 4.10E−61 A24 Mup12 Gm269171 8.37E−65 0.787057247 0.391 0.183 2.08E−60 A24 Gm26917 Dnajc3 2.12E−64 0.38898869 0.85 0.808 5.26E−60 A24 Dnajc3 Hao1 7.24E−61 0.391622737 0.83 0.767 1.80E−56 A24 Hao1 Pdia61 8.25E−60 0.420925025 0.779 0.702 2.05E−55 A24 Pdia6 Apob1 9.57E−60 0.353979053 0.983 0.99 2.38E−55 A24 Apob Manf 2.64E−58 0.465253736 0.632 0.478 6.55E−54 A24 Manf Pdcd41 4.76E−58 0.46790935 0.677 0.542 1.18E−53 A24 Pdcd4 AI1823711 9.61E−58 0.423055602 0.747 0.654 2.39E−53 A24 AI182371 Comt1 5.49E−57 0.302019368 0.928 0.92 1.36E−52 A24 Comt Cpb21 2.17E−56 0.331551897 0.879 0.827 5.40E−52 A24 Cpb2 Serp1 2.18E−55 0.402045023 0.809 0.725 5.42E−51 A24 Serp1 Cml21 5.80E−55 0.34556361 0.896 0.849 1.44E−50 A24 Cml2 Elovl2 1.73E−53 0.380671427 0.826 0.751 4.29E−49 A24 Elovl2 mmu-mir-62361 6.37E−53 0.845892758 0.896 0.843 1.58E−48 A24 mmu-mir-6236 Iigp11 1.35E−52 0.333549341 0.832 0.798 3.36E−48 A24 Iigp1 Calm1 1.03E−50 0.370158531 0.794 0.759 2.56E−46 A24 Calm1 Cps1 2.48E−50 0.277513678 0.982 0.977 6.16E−46 A24 Cps1 Eif4g21 6.14E−50 0.351474078 0.8 0.739 1.52E−45 A24 Eif4g2 Acox1 1.63E−48 0.274311383 0.966 0.968 4.05E−44 A24 Acox1 Fndc3b1 3.80E−48 0.320238213 0.291 0.125 9.44E−44 A24 Fndc3b Slc41a2 1.01E−47 0.28795823 0.302 0.132 2.51E−43 A24 Slc41a2 Nr1d2 5.02E−47 0.385472609 0.442 0.263 1.25E−42 A24 Nr1d2 Insig1 1.30E−46 0.412470778 0.626 0.487 3.23E−42 A24 Insig1 Aox31 1.16E−45 0.348891224 0.916 0.896 2.88E−41 A24 Aox3 Spcs3 6.70E−45 0.390709307 0.483 0.325 1.66E−40 A24 Spcs3 Atxn1 2.39E−44 0.325041158 0.311 0.148 5.93E−40 A24 Atxn1 Cmah 3.14E−44 0.424294686 0.607 0.472 7.80E−40 A24 Cmah Pnpla7 4.00E−44 0.396590342 0.678 0.561 9.93E−40 A24 Pnpla7 Dnajc12 1.33E−42 0.324049682 0.275 0.125 3.31E−38 A24 Dnajc12 Atp8b1 3.45E−42 0.361014487 0.391 0.221 8.56E−38 A24 Atp8b1 Hspa13 3.59E−42 0.341967618 0.404 0.237 8.92E−38 A24 Hspa13 AA4744081 1.41E−41 0.414816707 0.278 0.126 3.51E−37 A24 AA474408 Canx 1.09E−40 0.277059295 0.872 0.862 2.70E−36 A24 Canx Tmed7 1.35E−40 0.371496345 0.563 0.417 3.35E−36 A24 Tmed7 Il13ra1 1.42E−40 0.288909598 0.33 0.168 3.53E−36 A24 Il13ra1 Sdf2l1 2.54E−40 0.307771718 0.412 0.24 6.31E−36 A24 Sdf2l1 Acly 5.13E−40 0.410128052 0.597 0.448 1.27E−35 A24 Acly Cxcl11 8.60E−40 0.453014277 0.482 0.315 2.14E−35 A24 Cxcl1 Prg4 3.70E−39 0.400695342 0.421 0.254 9.19E−35 A24 Prg4 Adh41 9.82E−39 0.391972485 0.667 0.538 2.44E−34 A24 Adh4 Lrg11 4.41E−38 0.30956022 0.849 0.786 1.09E−33 A24 Lrg1 Hsd17b21 1.09E−37 0.323137514 0.758 0.682 2.72E−33 A24 Hsd17b2 Hsd3b51 1.25E−36 0.30091435 0.638 0.451 3.10E−32 A24 Hsd3b5 Hs3st3b1 3.00E−36 0.321902053 0.442 0.286 7.44E−32 A24 Hs3st3b1 Rpn1 3.41E−36 0.399145856 0.605 0.494 8.47E−32 A24 Rpn1 Tmem30a 9.46E−36 0.305621509 0.766 0.712 2.35E−31 A24 Tmem30a Rrbp1 2.26E−35 0.296754853 0.823 0.794 5.62E−31 A24 Rrbp1 Cyb5r3 9.28E−35 0.309656426 0.8 0.757 2.30E−30 A24 Cyb5r3 Hnf4a1 9.32E−34 0.254948257 0.85 0.799 2.31E−29 A24 Hnf4a Fos 1.67E−33 0.363187233 0.654 0.54 4.16E−29 A24 Fos Abca11 3.07E−33 0.383089812 0.556 0.428 7.62E−29 A24 Abca1 Cltc1 1.19E−32 0.33966836 0.61 0.485 2.96E−28 A24 Cltc Qsox1 6.53E−32 0.281749774 0.784 0.741 1.62E−27 A24 Qsox1 Lrp1 2.33E−31 0.483743655 0.694 0.626 5.78E−27 A24 Lrp1 Mlec 2.33E−31 0.340526351 0.496 0.361 5.78E−27 A24 Mlec Ssr1 3.21E−31 0.312867678 0.523 0.389 7.96E−27 A24 Ssr1 Nrp11 1.23E−30 0.329978654 0.426 0.278 3.05E−26 A24 Nrp1 Ostc 3.89E−30 0.308187678 0.514 0.373 9.65E−26 A24 Ostc Kmo1 9.66E−30 0.268702408 0.778 0.756 2.40E−25 A24 Kmo Ctnnb1 7.11E−29 0.328983549 0.566 0.457 1.77E−24 A24 Ctnnb1 Uggt1 9.70E−29 0.280537946 0.385 0.245 2.41E−24 A24 Uggt1 Gjb21 1.47E−28 0.29979701 0.709 0.635 3.66E−24 A24 Gjb2 Uso1 2.20E−28 0.320233643 0.597 0.51 5.47E−24 A24 Uso1 Slc3a1 2.88E−28 0.30743968 0.378 0.24 7.15E−24 A24 Slc3a1 Efna1 5.06E−28 0.316132363 0.482 0.361 1.26E−23 A24 Efna1 Usp9x 1.17E−27 0.338687365 0.502 0.378 2.91E−23 A24 Usp9x Sec61b1 2.12E−27 0.30077496 0.549 0.435 5.27E−23 A24 Sec61b Calu 4.28E−27 0.300472867 0.407 0.276 1.06E−22 A24 Calu Ak3 4.61E−27 0.250448075 0.772 0.74 1.14E−22 A24 Ak3 Nedd4 1.15E−26 0.330547905 0.647 0.583 2.86E−22 A24 Nedd4 Usp4 5.04E−26 0.295902719 0.476 0.347 1.25E−21 A24 Usp4 Gm54241 8.58E−26 0.2619882 0.445 0.309 2.13E−21 A24 Gm5424 Dhcr24 1.11E−25 0.282375698 0.857 0.827 2.77E−21 A24 Dhcr24 Rab1 1.32E−25 0.314483472 0.588 0.498 3.29E−21 A24 Rab1 Eif4g11 3.05E−25 0.276286732 0.745 0.715 7.57E−21 A24 Eif4g1 Acsl4 5.14E−25 0.299041198 0.478 0.365 1.28E−20 A24 Acsl4 Dnajb11 1.54E−24 0.328784649 0.557 0.467 3.83E−20 A24 Dnajb11 Srebf1 1.85E−24 0.314852133 0.439 0.319 4.59E−20 A24 Srebf1 Arcn1 1.92E−24 0.304399062 0.53 0.421 4.76E−20 A24 Arcn1 Copa 6.77E−24 0.333406263 0.525 0.417 1.68E−19 A24 Copa Mug21 1.27E−23 0.316623495 0.784 0.767 3.15E−19 A24 Mug2 Il6st 1.30E−23 0.301098452 0.448 0.329 3.23E−19 A24 Il6st Etnk1 2.89E−23 0.319444078 0.49 0.384 7.17E−19 A24 Etnk1 Prkd31 3.51E−23 0.304130117 0.631 0.557 8.72E−19 A24 Prkd3 Rdx1 4.33E−23 0.276007288 0.729 0.695 1.07E−18 A24 Rdx Ibtk 5.93E−23 0.295901316 0.43 0.312 1.47E−18 A24 Ibtk Lgr4 1.20E−22 0.257205387 0.399 0.279 2.99E−18 A24 Lgr4 Srpr 5.67E−22 0.291410089 0.532 0.442 1.41E−17 A24 Srpr Lman11 6.76E−22 0.251809068 0.75 0.697 1.68E−17 A24 Lman1 Edem1 1.41E−20 0.267537214 0.566 0.477 3.50E−16 A24 Edem1 Pten 1.56E−20 0.266292608 0.612 0.536 3.87E−16 A24 Pten Lrrc591 5.25E−20 0.268768371 0.449 0.341 1.30E−15 A24 Lrrc59 Srp72 6.96E−20 0.279992168 0.597 0.524 1.73E−15 A24 Srp72 Nars1 1.10E−19 0.312705274 0.593 0.534 2.74E−15 A24 Nars Ptprf1 1.19E−19 0.288833759 0.588 0.514 2.95E−15 A24 Ptprf Trip12 1.43E−19 0.283180183 0.504 0.407 3.54E−15 A24 Trip12 Mtus1 1.55E−19 0.312462778 0.563 0.485 3.85E−15 A24 Mtus1 Stard4 2.95E−19 0.292186548 0.559 0.471 7.32E−15 A24 Stard4 Proz 3.55E−19 0.27996652 0.622 0.56 8.83E−15 A24 Proz Txndc5 6.96E−19 0.275830553 0.48 0.378 1.73E−14 A24 Txndc5 Echdc1 8.90E−19 0.281783333 0.503 0.423 2.21E−14 A24 Echdc1 Gm242451 1.07E−18 0.41398979 0.369 0.262 2.65E−14 A24 Gm24245 Sec31a 1.72E−18 0.259599359 0.462 0.361 4.27E−14 A24 Sec31a Sh3bgrl 2.81E−18 0.26678946 0.512 0.42 6.99E−14 A24 Sh3bgrl Mtss1 4.50E−18 0.252212375 0.581 0.508 1.12E−13 A24 Mtss1 Sel1l 7.10E−18 0.283345281 0.544 0.46 1.76E−13 A24 Sel1l Ddost 8.86E−18 0.290898225 0.493 0.411 2.20E−13 A24 Ddost Slc38a10 2.68E−17 0.255657178 0.449 0.354 6.66E−13 A24 Slc38a10 Nab1 5.44E−17 0.260054412 0.491 0.398 1.35E−12 A24 Nab1 Nr5a2 9.20E−17 0.259898952 0.403 0.305 2.28E−12 A24 Nr5a2 Met 1.57E−16 0.251179491 0.434 0.344 3.91E−12 A24 Met Stt3b 1.78E−15 0.264816696 0.485 0.404 4.42E−11 A24 Stt3b Atp11c 2.49E−15 0.256760355 0.649 0.621 6.17E−11 A24 Atp11c Lasp1 2.85E−15 0.2607968 0.361 0.268 7.09E−11 A24 Lasp1 Grlf1 5.07E−15 0.255561206 0.413 0.321 1.26E−10 A24 Grlf1 Fam120a 2.45E−14 0.258279375 0.51 0.444 6.09E−10 A24 Fam120a Eprs1 1.69E−12 0.251287379 0.587 0.553 4.20E−08 A24 Eprs Lpgat11 2.69E−12 0.252503149 0.635 0.587 6.67E−08 A24 Lpgat1 Zbtb201 5.86E−12 0.313482745 0.566 0.513 1.46E−07 A24 Zbtb20 Fasn 5.64E−09 0.269895808 0.449 0.394 0.000140063 A24 Fasn Cyp4a142 0 1.280817508 0.991 0.5 0 A48 Cyp4a14 Mat1a2 0 0.775338592 1 0.97 0 A48 Mat1a Hmgcs22 0 0.768656201 1 0.977 0 A48 Hmgcs2 Apoe2  1.02E−282 0.504851654 1 1  2.53E−278 A48 Apoe Ces1c2  1.85E−278 0.548779002 0.999 0.984  4.59E−274 A48 Ces1c Cyp4a101  2.26E−270 0.932584678 0.991 0.643  5.62E−266 A48 Cyp4a10 Chchd102  1.01E−265 0.751681455 0.995 0.925  2.50E−261 A48 Chchd10 Apoc21  4.27E−263 0.863852376 0.98 0.8  1.06E−258 A48 Apoc2 Mfsd2a2  8.03E−247 0.661383645 0.731 0.203  1.99E−242 A48 Mfsd2a Ttc362  5.87E−246 0.563789091 0.996 0.93  1.46E−241 A48 Ttc36 Angptl32  1.51E−240 0.611080136 0.995 0.946  3.74E−236 A48 Angptl3 Apoh2  2.05E−235 0.462791749 0.998 0.979  5.10E−231 A48 Apoh Dbp  5.52E−234 0.289556365 0.52 0.091  1.37E−229 A48 Dbp Ahsg1  5.89E−227 0.359159618 1 0.999  1.46E−222 A48 Ahsg Vtn1  2.03E−225 0.522813418 1 0.98  5.04E−221 A48 Vtn Rgs16  5.76E−225 0.454464187 0.601 0.138  1.43E−220 A48 Rgs16 Retsat2  2.28E−218 0.709570556 0.988 0.827  5.66E−214 A48 Retsat Abcd2  2.96E−203 0.281300305 0.473 0.087  7.35E−199 A48 Abcd2 Agt1  5.52E−203 0.57952745 0.981 0.814  1.37E−198 A48 Agt Herpud11  1.06E−202 0.604376811 0.985 0.795  2.64E−198 A48 Herpud1 Aldob  1.64E−196 0.437497663 1 0.996  4.06E−192 A48 Aldob Serping11  3.48E−195 0.577711276 0.987 0.863  8.63E−191 A48 Serping1 Reep61  1.30E−193 0.623290477 0.967 0.791  3.24E−189 A48 Reep6 Apoa51  1.41E−191 0.44834918 0.998 0.961  3.49E−187 A48 Apoa5 Decr12  3.46E−191 0.566910147 0.96 0.678  8.60E−187 A48 Decr1 Slc25a472  1.27E−188 0.61748351 0.992 0.917  3.16E−184 A48 Slc25a47 F2  2.67E−188 0.395152093 0.999 0.969  6.63E−184 A48 F2 Rdh72  6.84E−187 0.468441105 0.996 0.958  1.70E−182 A48 Rdh7 Hrg1  3.57E−183 0.531568931 0.987 0.834  8.86E−179 A48 Hrg Rbp41  4.56E−183 0.394209205 1 0.997  1.13E−178 A48 Rbp4 Tef  4.84E−177 0.339416398 0.651 0.192  1.20E−172 A48 Tef Slco1a4  2.11E−176 0.509091975 0.77 0.291  5.23E−172 A48 Slco1a4 Gc  3.39E−175 0.297890227 1 0.998  8.41E−171 A48 Gc Gm6484  3.94E−173 0.410774201 0.627 0.191  9.79E−169 A48 Gm6484 Gm23935  1.27E−167 0.473837006 0.997 0.93  3.15E−163 A48 Gm23935 Ugt2b52  3.54E−167 0.438817409 0.996 0.942  8.78E−163 A48 Ugt2b5 Ttr2  2.12E−165 0.422488039 1 0.999  5.26E−161 A48 Ttr Rpl38  1.26E−162 0.332203899 0.596 0.173  3.14E−158 A48 Rpl38 St3gal52  9.27E−162 0.55492927 0.914 0.537  2.30E−157 A48 St3gal5 Lcat1  4.41E−155 0.505352395 0.973 0.77  1.10E−150 A48 Lcat Atp5h2  8.78E−153 0.597753903 0.933 0.64  2.18E−148 A48 Atp5h Apoc32  4.46E−151 0.406980262 1 0.977  1.11E−146 A48 Apoc3 Cp  1.69E−147 0.427391341 0.995 0.947  4.21E−143 A48 Cp Plin51  4.30E−146 0.398503015 0.788 0.332  1.07E−141 A48 Plin5 Prodh21  2.43E−145 0.505471452 0.918 0.598  6.02E−141 A48 Prodh2 Oaf1  3.43E−145 0.502082973 0.969 0.783  8.51E−141 A48 Oaf Scand1  3.53E−145 0.270683065 0.579 0.175  8.77E−141 A48 Scand1 Khk2  6.78E−145 0.520248448 0.982 0.855  1.68E−140 A48 Khk Hmgcl2  1.35E−144 0.550084606 0.956 0.723  3.36E−140 A48 Hmgcl Lims2  6.42E−144 0.376119911 0.679 0.253  1.59E−139 A48 Lims2 Pnpla21  9.86E−144 0.346497418 0.687 0.253  2.45E−139 A48 Pnpla2 Sult1a11  4.81E−142 0.482660126 0.963 0.718  1.20E−137 A48 Sult1a1 Fth1  1.45E−141 0.37500962 0.996 0.975  3.60E−137 A48 Fth1 Lpin11  9.79E−141 0.514964358 0.736 0.315  2.43E−136 A48 Lpin1 Hdac111  4.34E−139 0.355729038 0.713 0.277  1.08E−134 A48 Hdac11 Syvn1  4.46E−139 0.304118127 0.603 0.201  1.11E−134 A48 Syvn1 Ttpa  1.70E−138 0.443146694 0.991 0.876  4.23E−134 A48 Ttpa Nr1i32  3.96E−138 0.47586273 0.814 0.371  9.85E−134 A48 Nr1i3 Fkbp51  1.26E−136 0.257227973 0.54 0.158  3.12E−132 A48 Fkbp5 Ephx21  6.88E−135 0.386872421 0.993 0.919  1.71E−130 A48 Ephx2 Snord1181  9.71E−135 0.477121215 0.766 0.324  2.41E−130 A48 Snord118 Slc27a51  3.81E−134 0.406176884 0.987 0.885  9.45E−130 A48 Slc27a5 Ces1b  1.19E−132 0.482951665 0.838 0.445  2.95E−128 A48 Ces1b Ndrg21  1.81E−132 0.348203765 1 0.939  4.50E−128 A48 Ndrg2 Cox8a2  3.15E−131 0.552001416 0.89 0.599  7.83E−127 A48 Cox8a Cyp2a12  1.00E−129 0.466431941 0.981 0.879  2.49E−125 A48 Cyp2a12 Cyp3a252  2.18E−129 0.360731032 0.995 0.902  5.41E−125 A48 Cyp3a25 Ambp  5.70E−128 0.285979982 1 0.991  1.42E−123 A48 Ambp Pabpc1  5.17E−127 0.478200371 0.912 0.629  1.28E−122 A48 Pabpc1 Mlycd1  9.54E−127 0.43784239 0.893 0.5  2.37E−122 A48 Mlycd F101  1.50E−125 0.392724712 0.989 0.886  3.73E−121 A48 F10 Gys21  2.76E−124 0.423060822 0.784 0.376  6.84E−120 A48 Gys2 Cdo11  1.19E−123 0.397073051 0.997 0.956  2.96E−119 A48 Cdo1 Echs11  2.01E−123 0.464869604 0.971 0.806  5.00E−119 A48 Echs1 Bnip32  3.06E−123 0.462029744 0.876 0.529  7.61E−119 A48 Bnip3 Slc37a41  4.81E−123 0.446122628 0.858 0.484  1.19E−118 A48 Slc37a4 Tmbim61  1.33E−122 0.371305411 0.996 0.943  3.30E−118 A48 Tmbim6 Bfar  3.12E−122 0.308011346 0.742 0.306  7.75E−118 A48 Bfar Ube2r21  4.52E−122 0.442298634 0.884 0.54  1.12E−117 A48 Ube2r2 Abcb41  2.99E−121 0.442520105 0.956 0.688  7.42E−117 A48 Abcb4 Grn1  6.37E−120 0.431036339 0.844 0.449  1.58E−115 A48 Grn Slc25a102  3.22E−119 0.431271222 0.877 0.526  8.00E−115 A48 Slc25a10 Hpx1  7.59E−118 0.385111507 0.999 0.997  1.89E−113 A48 Hpx Vnn3  4.99E−116 0.300835625 0.684 0.275  1.24E−111 A48 Vnn3 Fcgrt1  2.63E−115 0.408442054 0.91 0.576  6.53E−111 A48 Fcgrt Fah1  8.72E−115 0.391286468 0.974 0.821  2.17E−110 A48 Fah Atp5b  1.69E−114 0.328113534 0.997 0.94  4.19E−110 A48 Atp5b Amy12  4.53E−114 0.421579258 0.943 0.66  1.13E−109 A48 Amy1 Gstt3  3.70E−113 0.338366426 0.737 0.312  9.19E−109 A48 Gstt3 Ech11  1.29E−112 0.418013348 0.98 0.828  3.21E−108 A48 Ech1 Hsd17b131  1.32E−112 0.622071742 0.934 0.741  3.29E−108 A48 Hsd17b13 Serpina3m1  6.99E−112 0.40339321 0.949 0.749  1.74E−107 A48 Serpina3m Serpina1d2  2.32E−111 0.30529594 0.997 0.977  5.77E−107 A48 Serpina1d Decr21  2.53E−109 0.412881852 0.92 0.644  6.29E−105 A48 Decr2 Hspa82  5.67E−109 0.410735253 0.952 0.731  1.41E−104 A48 Hspa8 Gltscr2  1.30E−108 0.343207156 0.83 0.435  3.24E−104 A48 Gltscr2 Slc25a20  2.03E−108 0.387540813 0.877 0.508  5.03E−104 A48 Slc25a20 Abhd14b1  5.35E−108 0.405910897 0.885 0.554  1.33E−103 A48 Abhd14b Cebpb2  2.85E−107 0.368375731 0.815 0.414  7.09E−103 A48 Cebpb Ahcy1  6.37E−107 0.339983635 0.988 0.875  1.58E−102 A48 Ahcy F12  9.50E−107 0.388008981 0.966 0.803  2.36E−102 A48 F12 Cox5a1  2.15E−106 0.41972236 0.938 0.693  5.34E−102 A48 Cox5a Tcea31  3.05E−106 0.39376107 0.825 0.448  7.58E−102 A48 Tcea3 Tmbim41  6.73E−106 0.369287383 0.784 0.407  1.67E−101 A48 Tmbim4 Acad11  1.16E−105 0.38508652 0.896 0.583  2.88E−101 A48 Acad11 Gabarap1  8.50E−105 0.40143345 0.956 0.75  2.11E−100 A48 Gabarap Aldh9a1  9.77E−105 0.382553818 0.964 0.772  2.43E−100 A48 Aldh9a1 Ddb1  2.16E−103 0.354415928 0.83 0.452 5.37E−99 A48 Ddb1 P4hb2  5.46E−103 0.298062011 0.995 0.942 1.36E−98 A48 P4hb Yipf3  1.81E−102 0.278463646 0.68 0.291 4.50E−98 A48 Yipf3 Sh3glb1  9.56E−102 0.304360744 0.695 0.306 2.37E−97 A48 Sh3glb1 Rpl4  2.39E−101 0.328862408 0.987 0.912 5.93E−97 A48 Rpl4 Ctsh1  2.95E−101 0.422416234 0.945 0.72 7.32E−97 A48 Ctsh Apoa41  1.97E−100 0.494713556 0.778 0.4 4.90E−96 A48 Apoa4 Mgll  3.72E−100 0.365109404 0.844 0.477 9.23E−96 A48 Mgll Ppara1  6.73E−100 0.339317968 0.831 0.443 1.67E−95 A48 Ppara 1600002H07Rik 1.17E−98 0.30157504 0.736 0.353 2.91E−94 A48 1600002H07Rik G0s21 1.31E−98 0.387970035 0.692 0.32 3.26E−94 A48 G0s2 Cox6a12 1.81E−98 0.371822664 0.987 0.854 4.49E−94 A48 Cox6a1 Igfbp4 6.46E−98 0.339536078 0.99 0.875 1.60E−93 A48 Igfbp4 C4b1 2.60E−97 0.398907532 0.975 0.876 6.46E−93 A48 C4b Sdhc 2.46E−96 0.38650315 0.91 0.645 6.10E−92 A48 Sdhc Apoc42 3.94E−96 0.409636949 0.998 0.965 9.79E−92 A48 Apoc4 Serpinf1 4.30E−96 0.356520958 0.976 0.855 1.07E−91 A48 Serpinf1 Wbp1l1 7.44E−96 0.38750996 0.91 0.648 1.85E−91 A48 Wbp1l Aldoa 1.89E−95 0.277740845 0.719 0.329 4.70E−91 A48 Aldoa Atp5k1 2.67E−95 0.384272907 0.935 0.664 6.63E−91 A48 Atp5k Aspdh 5.69E−95 0.321708599 0.776 0.397 1.41E−90 A48 Aspdh Gm2a 4.55E−94 0.349188726 0.827 0.459 1.13E−89 A48 Gm2a Etnppl2 1.17E−93 0.525305142 0.866 0.587 2.89E−89 A48 Etnppl Etfb1 8.54E−93 0.309173682 0.996 0.928 2.12E−88 A48 Etfb Sec14l21 1.30E−92 0.352363823 0.98 0.835 3.23E−88 A48 Sec14l2 Camk2n11 2.32E−92 0.273006774 0.691 0.315 5.77E−88 A48 Camk2n1 Slc10a11 2.86E−92 0.375331232 0.984 0.84 7.10E−88 A48 Slc10a1 Ifnar2 6.13E−92 0.274914839 0.731 0.34 1.52E−87 A48 Ifnar2 Cpt2 8.07E−92 0.326691619 0.807 0.437 2.00E−87 A48 Cpt2 Azgp1 2.23E−91 0.252008502 0.997 0.966 5.53E−87 A48 Azgp1 Uroc1 1.35E−90 0.407426649 0.914 0.637 3.34E−86 A48 Uroc1 Pbld11 6.93E−90 0.345326717 0.881 0.566 1.72E−85 A48 Pbld1 Brap 1.06E−89 0.315930007 0.829 0.465 2.62E−85 A48 Brap Shmt11 1.20E−89 0.347962893 0.882 0.556 2.98E−85 A48 Shmt1 Slc27a2 1.39E−89 0.313906428 0.996 0.945 3.44E−85 A48 Slc27a2 Asgr21 7.88E−89 0.348507534 0.879 0.552 1.96E−84 A48 Asgr2 Aco2 3.32E−88 0.326709931 0.846 0.507 8.24E−84 A48 Aco2 Ctsd 1.28E−87 0.354466764 0.916 0.642 3.17E−83 A48 Ctsd Cyp3a112 3.21E−87 0.397040898 1 0.995 7.98E−83 A48 Cyp3a11 Sdhd2 4.40E−87 0.434718095 0.891 0.655 1.09E−82 A48 Sdhd 0610005C13Rik1 6.63E−86 0.335559673 0.944 0.665 1.65E−81 A48 0610005C13Rik Slc40a11 9.34E−86 0.272553886 0.744 0.367 2.32E−81 A48 Slc40a1 Cyp2c441 1.12E−85 0.414935231 0.924 0.692 2.77E−81 A48 Cyp2c44 Lamp11 1.61E−85 0.327385277 0.982 0.877 4.01E−81 A48 Lamp1 Creb3l3 5.60E−85 0.330494287 0.971 0.818 1.39E−80 A48 Creb3l3 Pigr 1.16E−84 0.40014252 0.977 0.945 2.89E−80 A48 Pigr Apoc12 4.87E−84 0.292819411 1 0.992 1.21E−79 A48 Apoc1 Smlr11 5.67E−84 0.251582244 0.68 0.317 1.41E−79 A48 Sm1r1 Snx3 7.63E−84 0.256302059 0.693 0.331 1.89E−79 A48 Snx3 Atp5g31 1.55E−83 0.328843609 0.985 0.888 3.85E−79 A48 Atp5g3 Cyp2d26 4.14E−83 0.305047306 0.982 0.897 1.03E−78 A48 Cyp2d26 Klf9 4.69E−83 0.332611254 0.862 0.549 1.17E−78 A48 Klf9 Eci2 5.28E−83 0.328111149 0.944 0.697 1.31E−78 A48 Eci2 Slc2a21 7.42E−83 0.356962096 0.824 0.485 1.84E−78 A48 Slc2a2 Acot12 6.96E−82 0.278479827 0.825 0.454 1.73E−77 A48 Acot12 Tmem120a 1.04E−81 0.252496012 0.708 0.343 2.59E−77 A48 Tmem120a Pglyrp2 6.41E−81 0.307416307 0.754 0.402 1.59E−76 A48 Pglyrp2 Abcc3 1.62E−80 0.35576814 0.859 0.549 4.03E−76 A48 Abcc3 Fam195a1 4.52E−80 0.286110606 0.726 0.359 1.12E−75 A48 Fam195a Ctsa 8.45E−80 0.25495645 0.731 0.36 2.10E−75 A48 Ctsa Oplah 1.28E−79 0.303362318 0.805 0.457 3.19E−75 A48 Oplah Acat11 4.32E−79 0.307325333 0.978 0.842 1.07E−74 A48 Acat1 Park71 3.18E−78 0.343705589 0.953 0.774 7.89E−74 A48 Park7 Pbld2 4.10E−78 0.312075493 0.891 0.58 1.02E−73 A48 Pbld2 Serpina3n1 9.63E−78 0.318139347 0.902 0.626 2.39E−73 A48 Serpina3n Serinc31 3.42E−77 0.289735353 0.793 0.452 8.48E−73 A48 Serinc3 Pitpnb 8.76E−77 0.266116041 0.795 0.431 2.18E−72 A48 Pitpnb Usmg52 9.41E−77 0.376132402 0.755 0.419 2.34E−72 A48 Usmg5 Ninj11 9.74E−77 0.346226664 0.874 0.587 2.42E−72 A48 Ninj1 Hsd17b102 2.43E−76 0.404734527 0.927 0.686 6.03E−72 A48 Hsd17b10 Eef1d 6.80E−75 0.257204457 0.795 0.434 1.69E−70 A48 Eef1d Lipa1 2.40E−74 0.31862164 0.904 0.63 5.96E−70 A48 Lipa Agpat6 3.14E−74 0.289480086 0.884 0.558 7.81E−70 A48 Agpat6 Pim31 3.82E−74 0.313735047 0.845 0.52 9.48E−70 A48 Pim3 Pcx 5.84E−74 0.315978553 0.912 0.66 1.45E−69 A48 Pcx Creg11 3.96E−73 0.2979552 0.993 0.917 9.83E−69 A48 Creg1 Gcdh1 4.36E−73 0.288485226 0.977 0.848 1.08E−68 A48 Gcdh Atp5d1 1.54E−72 0.307608726 0.935 0.694 3.81E−68 A48 Atp5d Gfra11 1.91E−72 0.288958416 0.867 0.539 4.74E−68 A48 Gfra1 Pck11 2.03E−72 0.350075486 0.999 0.974 5.03E−68 A48 Pck1 Gstt2 1.93E−71 0.25926769 0.754 0.398 4.80E−67 A48 Gstt2 Sord1 3.59E−71 0.301872945 0.987 0.917 8.92E−67 A48 Sord Tmem371 7.54E−71 0.261063123 0.786 0.429 1.87E−66 A48 Tmem37 Pla2g12b 8.56E−71 0.27882702 0.798 0.457 2.13E−66 A48 Pla2g12b Ndufb22 1.82E−70 0.348400962 0.888 0.589 4.53E−66 A48 Ndufb2 Atf5 2.73E−70 0.317193075 0.909 0.649 6.78E−66 A48 Atf5 Sfxn1 2.87E−70 0.329269537 0.822 0.522 7.13E−66 A48 Sfxn1 Glrx52 3.18E−70 0.299962013 0.886 0.568 7.89E−66 A48 Glrx5 Atp5j1 2.90E−69 0.350683282 0.916 0.73 7.19E−65 A48 Atp5j Ggnbp2 3.08E−69 0.257783021 0.818 0.458 7.65E−65 A48 Ggnbp2 Furin 4.55E−69 0.280556705 0.781 0.445 1.13E−64 A48 Furin Ndufb101 7.41E−69 0.316418226 0.907 0.669 1.84E−64 A48 Ndufb10 Dhrs41 1.15E−68 0.276531082 0.94 0.671 2.87E−64 A48 Dhrs4 Sec61a1 1.50E−68 0.289912357 0.825 0.513 3.72E−64 A48 Sec61a1 Zfp91 1.51E−68 0.275372132 0.855 0.531 3.75E−64 A48 Zfp91 D17Wsu92e 1.81E−68 0.282647467 0.909 0.62 4.49E−64 A48 D17Wsu92e Sult1d12 2.07E−68 0.43989704 0.936 0.68 5.14E−64 A48 Sult1d1 Mst1 3.99E−68 0.277541098 0.81 0.489 9.91E−64 A48 Mst1 Igf1 7.06E−68 0.302677789 0.985 0.902 1.75E−63 A48 Igf1 Acadvl 8.03E−68 0.280297075 0.959 0.782 1.99E−63 A48 Acadvl Hgfac 1.41E−67 0.265617858 0.786 0.457 3.49E−63 A48 Hgfac 11-Mar 1.82E−67 0.28124308 0.984 0.869 4.51E−63 A48 1-Mar Tgoln1 4.48E−67 0.305516812 0.891 0.602 1.11E−62 A48 Tgoln1 Upb11 4.61E−67 0.305876376 0.945 0.746 1.14E−62 A48 Upb1 Acbd51 7.35E−67 0.284090869 0.943 0.711 1.82E−62 A48 Acbd5 Sds2 2.26E−66 0.553946754 0.799 0.612 5.62E−62 A48 Sds Map2k2 2.40E−66 0.255067193 0.832 0.517 5.96E−62 A48 Map2k2 Ndufs71 2.84E−66 0.254510701 0.847 0.51 7.05E−62 A48 Ndufs7 Dcxr2 3.22E−66 0.298871488 0.884 0.591 7.99E−62 A48 Dcxr Gpt1 3.35E−66 0.288097988 0.94 0.737 8.32E−62 A48 Gpt Gpld1 6.68E−66 0.288714573 0.877 0.595 1.66E−61 A48 Gpld1 1100001G20Rik1 7.71E−66 0.341544398 0.993 0.968 1.91E−61 A48 110000 1G20Rik Ndufs81 2.39E−65 0.314878255 0.854 0.581 5.94E−61 A48 Ndufs8 Abca6 5.35E−65 0.284030069 0.849 0.548 1.33E−60 A48 Abca6 Actn4 4.59E−64 0.25335849 0.789 0.465 1.14E−59 A48 Actn4 Gchfr2 2.18E−63 0.323950621 0.953 0.727 5.42E−59 A48 Gchfr Mia3 6.64E−63 0.284751778 0.91 0.64 1.65E−58 A48 Mia3 Cd1d11 8.52E−63 0.292681939 0.887 0.611 2.11E−58 A48 Cd1d1 Tmem176b1 9.86E−63 0.288247134 0.89 0.63 2.45E−58 A48 Tmem176b Lpin21 1.01E−62 0.304127419 0.921 0.653 2.52E−58 A48 Lpin2 Pccb 1.17E−62 0.280165918 0.901 0.642 2.90E−58 A48 Pccb Cideb2 1.52E−62 0.315951718 0.892 0.65 3.79E−58 A48 Cideb Itih1 2.19E−62 0.288782591 0.974 0.819 5.45E−58 A48 Itih1 B2m2 2.44E−62 0.257225676 0.997 0.949 6.06E−58 A48 B2m Maob 5.02E−62 0.288484521 0.889 0.597 1.25E−57 A48 Maob Slc25a39 6.32E−62 0.295889572 0.938 0.762 1.57E−57 A48 Slc25a39 Acadl 9.46E−62 0.260302089 0.916 0.643 2.35E−57 A48 Acadl Hadh1 1.41E−61 0.279987697 0.908 0.641 3.49E−57 A48 Hadh Akr1c191 5.83E−61 0.295184218 0.821 0.507 1.45E−56 A48 Akr1c19 Os9 1.17E−60 0.268248599 0.911 0.673 2.90E−56 A48 Os9 Pemt1 1.39E−60 0.316750177 0.948 0.754 3.46E−56 A48 Pemt Hsbp11 1.15E−59 0.2547665 0.792 0.495 2.86E−55 A48 Hsbp1 Serpinf2 2.36E−59 0.262659763 0.966 0.847 5.86E−55 A48 Serpinf2 Ndufa131 6.13E−59 0.286435118 0.959 0.769 1.52E−54 A48 Ndufa13 Gsto1 6.52E−59 0.279937059 0.818 0.518 1.62E−54 A48 Gsto1 Ubxn4 2.22E−58 0.25604972 0.893 0.601 5.52E−54 A48 Ubxn4 Slc25a13 2.47E−58 0.263619116 0.924 0.668 6.14E−54 A48 Slc25a13 Hadha 3.06E−58 0.279003545 0.943 0.743 7.60E−54 A48 Hadha Surf4 3.88E−58 0.252260406 0.873 0.578 9.64E−54 A48 Surf4 Hal1 4.19E−58 0.382660599 0.908 0.741 1.04E−53 A48 Ha1 Akr1d11 1.29E−57 0.264802354 0.852 0.543 3.22E−53 A48 Akr1d1 Rabac12 5.41E−56 0.250868483 0.807 0.498 1.34E−51 A48 Rabac1 Tspo1 7.02E−56 0.266009062 0.784 0.477 1.74E−51 A48 Tspo Mttp 9.90E−56 0.261697738 0.933 0.709 2.46E−51 A48 Mttp Ctage5 2.71E−55 0.27450678 0.941 0.698 6.74E−51 A48 Ctage5 Agpat3 3.06E−55 0.25259632 0.874 0.617 7.61E−51 A48 Agpat3 Gamt1 3.37E−55 0.268064254 0.841 0.564 8.36E−51 A48 Gamt Dgat21 3.63E−55 0.26370048 0.947 0.753 9.02E−51 A48 Dgat2 Sardh 7.35E−53 0.278384633 0.959 0.829 1.82E−48 A48 Sardh Asl1 2.33E−51 0.336107029 0.953 0.801 5.79E−47 A48 Asl Acsl12 5.59E−51 0.254529662 0.978 0.895 1.39E−46 A48 Acsl1 Ccs1 9.34E−50 0.264321005 0.895 0.655 2.32E−45 A48 Ccs BC089597 1.42E−49 0.250990415 0.813 0.516 3.52E−45 A48 BC089597 Por2 5.03E−49 0.289329631 0.921 0.688 1.25E−44 A48 Por Uqcrfs1 6.79E−48 0.257925751 0.949 0.781 1.69E−43 A48 Uqcrfs1 Hagh1 4.03E−47 0.287377171 0.959 0.834 1.00E−42 A48 Hagh Tmem14c1 5.76E−47 0.250667772 0.837 0.561 1.43E−42 A48 Tmem14c Dak 5.90E−47 0.296630929 0.852 0.575 1.47E−42 A48 Dak Leap22 2.60E−44 0.335628781 0.833 0.576 6.45E−40 A48 Leap2 Cpt1a 1.94E−43 0.264989382 0.896 0.681 4.81E−39 A48 Cpt1a Mpc22 1.37E−42 0.287450301 0.953 0.826 3.40E−38 A48 Mpc2 Cd3021 6.25E−40 0.271235165 0.956 0.844 1.55E−35 A48 Cd302 Rps27l2 8.74E−39 0.286856723 0.924 0.795 2.17E−34 A48 Rps27l Cyp2f21 3.99E−31 0.296079879 0.912 0.833 9.91E−27 A48 Cyp2f2 Slc7a2 3.98E−30 0.250213104 0.921 0.758 9.87E−26 A48 Slc7a2 Glul 2.05E−13 0.540145967 0.308 0.18 5.09E−09 A48 Glul Apoc13  1.14E−259 0.549525053 1 0.992  2.84E−255 A96 Apoc1 Cyp4a143  2.66E−250 0.970243185 0.975 0.511  6.60E−246 A96 Cyp4a14 Cyp4a102  2.15E−216 0.868151957 0.974 0.651  5.34E−212 A96 Cyp4a10 Mat1a3  3.10E−210 0.596679364 1 0.97  7.70E−206 A96 Mat1a Angptl33  5.10E−206 0.560557268 0.998 0.946  1.27E−201 A96 Angptl3 Cdo12  3.07E−182 0.508585858 0.998 0.957  7.61E−178 A96 Cdo1 Apoa22  2.85E−177 0.344745894 1 0.999  7.07E−173 A96 Apoa2 Zfp683  2.01E−176 0.41843816 0.476 0.092  4.99E−172 A96 Zfp683 Apoe3  2.87E−148 0.316142135 1 1  7.13E−144 A96 Apoe Chchd103  1.38E−138 0.47683652 0.994 0.927  3.43E−134 A96 Chchd10 Ttr3  2.28E−137 0.317447356 1 0.999  5.66E−133 A96 Ttr Ttpa1  4.82E−129 0.492631097 0.98 0.879  1.20E−124 A96 Ttpa Scd12  2.34E−118 0.520262727 0.989 0.926  5.82E−114 A96 Scd1 Ubc2  2.86E−109 0.480972081 0.968 0.839  7.10E−105 A96 Ubc Apoh3  2.32E−107 0.308461461 0.998 0.979  5.76E−103 A96 Apoh Ces1d1  9.98E−105 0.450848726 0.977 0.905  2.48E−100 A96 Ces1d Apoc33  1.84E−102 0.338145432 1 0.978 4.56E−98 A96 Apoc3 Ces1c3 8.24E−97 0.298285129 1 0.985 2.05E−92 A96 Ces1c Hmgcs23 2.29E−95 0.304092138 0.996 0.977 5.70E−91 A96 Hmgcs2 Slco1b21 3.01E−92 0.515680504 0.998 0.929 7.48E−88 A96 Slco1b2 Cyp8b12 6.15E−88 0.516691772 0.897 0.691 1.53E−83 A96 Cyp8b1 Hamp2 4.13E−86 0.548864769 0.92 0.788 1.03E−81 A96 Hamp Slc27a21 7.10E−80 0.325141901 0.988 0.947 1.76E−75 A96 Slc27a2 Hspa83 1.35E−77 0.414165913 0.905 0.741 3.34E−73 A96 Hspa8 Mettl7b1 3.18E−76 0.370125266 0.949 0.866 7.90E−72 A96 Mettl7b Cyp3a113 1.94E−75 0.275004032 0.999 0.995 4.82E−71 A96 Cyp3a11 Crot1 7.79E−75 0.314330235 0.989 0.942 1.94E−70 A96 Crot Cyp2c292 1.44E−68 0.551021967 0.962 0.85 3.59E−64 A96 Cyp2c29 Acbd52 3.67E−64 0.390303062 0.87 0.725 9.12E−60 A96 Acbd5 Acsl13 2.22E−63 0.329698108 0.977 0.897 5.52E−59 A96 Acsl1 Sult1a12 2.88E−62 0.384980426 0.881 0.733 7.15E−58 A96 Sult1a1 Aldh2 6.54E−62 0.2825177 0.995 0.968 1.62E−57 A96 Aldh2 Retsat3 2.39E−61 0.365551797 0.957 0.834 5.92E−57 A96 Retsat Abcb42 3.19E−61 0.389954192 0.878 0.704 7.92E−57 A96 Abcb4 Ndrg22 1.13E−60 0.2700141 0.985 0.942 2.81E−56 A96 Ndrg2 Aldh3a22 3.23E−60 0.565894922 0.687 0.451 8.02E−56 A96 Aldh3a2 Atp5k2 9.30E−60 0.371467827 0.837 0.682 2.31E−55 A96 Atp5k Amy13 2.54E−58 0.386150545 0.831 0.681 6.31E−54 A96 Amy1 Igfbp41 2.23E−56 0.295776474 0.964 0.881 5.53E−52 A96 Igfbp4 Chpt11 2.52E−56 0.380201964 0.848 0.694 6.27E−52 A96 Chpt1 Pex11a1 4.35E−56 0.446250068 0.7 0.484 1.08E−51 A96 Pex11a Hhex1 7.20E−54 0.355789479 0.543 0.313 1.79E−49 A96 Hhex Sult1d13 2.09E−51 0.389921134 0.855 0.696 5.20E−47 A96 Sult1d1 Atp5h3 1.30E−50 0.314445524 0.848 0.657 3.24E−46 A96 Atp5h Cyp3a253 5.89E−50 0.2702962 0.981 0.905 1.46E−45 A96 Cyp3a25 Lipa2 1.77E−49 0.355944215 0.791 0.651 4.41E−45 A96 Lipa Cyp2e12 4.42E−49 0.511826271 0.93 0.809 1.10E−44 A96 Cyp2e1 Prlr 2.34E−48 0.346406091 0.574 0.359 5.82E−44 A96 Prlr Clpx1 3.44E−48 0.325403599 0.884 0.764 8.54E−44 A96 Clpx Tmem56 4.52E−47 0.334247655 0.812 0.643 1.12E−42 A96 Tmem56 Insig22 1.46E−46 0.285386985 0.928 0.818 3.63E−42 A96 Insig2 Hrg2 6.03E−46 0.280535908 0.923 0.845 1.50E−41 A96 Hrg Ube2r22 1.09E−45 0.338184842 0.747 0.565 2.70E−41 A96 Ube2r2 Ppp2r5a1 3.21E−45 0.350536833 0.764 0.615 7.96E−41 A96 Ppp2r5a Nr1i33 6.04E−44 0.348125519 0.625 0.405 1.50E−39 A96 Nr1i3 Cox6a13 9.03E−44 0.274547323 0.943 0.862 2.24E−39 A96 Cox6a1 Creg12 1.75E−43 0.251687315 0.985 0.919 4.34E−39 A96 Creg1 Acaa1b2 3.05E−43 0.281984752 0.986 0.919 7.56E−39 A96 Acaa1b Cyp7a1 1.08E−42 0.378826941 0.398 0.199 2.68E−38 A96 Cyp7a1 Cyp2c542 1.49E−42 0.344687089 0.86 0.726 3.70E−38 A96 Cyp2c54 Cyp2c502 4.24E−42 0.324188529 0.943 0.847 1.05E−37 A96 Cyp2c50 Snord1182 9.05E−42 0.378239005 0.564 0.36 2.25E−37 A96 Snord118 Asl2 9.71E−42 0.275035314 0.896 0.811 2.41E−37 A96 Asl Csad2 9.95E−42 0.420651804 0.843 0.684 2.47E−37 A96 Csad Sc4mol2 2.31E−41 0.336092423 0.781 0.631 5.74E−37 A96 Sc4mol Igfbp13 2.40E−41 0.260251838 0.826 0.691 5.95E−37 A96 Igfbp1 Gabarapl11 6.61E−41 0.293237647 0.881 0.78 1.64E−36 A96 Gabarapl1 Tsc22d3 8.65E−41 0.336254391 0.534 0.338 2.15E−36 A96 Tsc22d3 Acot11 1.16E−40 0.310587102 0.459 0.257 2.88E−36 A96 Acot1 Gyk 2.01E−40 0.313401573 0.616 0.441 5.00E−36 A96 Gyk Decr22 3.24E−40 0.301753937 0.813 0.664 8.03E−36 A96 Decr2 Cth1 3.77E−40 0.296643035 0.944 0.826 9.37E−36 A96 Cth Pon12 4.32E−40 0.289869231 0.965 0.888 1.07E−35 A96 Pon1 Cd36 9.83E−40 0.312878157 0.299 0.131 2.44E−35 A96 Cd36 Aplp2 1.81E−39 0.290277561 0.826 0.67 4.48E−35 A96 Aplp2 Agpat61 2.42E−38 0.314279412 0.743 0.584 6.01E−34 A96 Agpat6 Agt2 2.70E−38 0.255008722 0.912 0.827 6.71E−34 A96 Agt Hmgcl3 1.80E−37 0.274375388 0.871 0.739 4.47E−33 A96 Hmgcl Gstt31 3.07E−37 0.302584013 0.541 0.347 7.61E−33 A96 Gstt3 Aqp91 3.47E−37 0.317770961 0.801 0.664 8.62E−33 A96 Aqp9 Akr1d12 6.11E−37 0.299364499 0.721 0.567 1.52E−32 A96 Akr1d1 Slc4a41 7.42E−37 0.297654558 0.609 0.42 1.84E−32 A96 Slc4a4 Ptms1 8.05E−37 0.286253315 0.806 0.71 2.00E−32 A96 Ptms Rgn2 9.16E−37 0.368626566 0.899 0.786 2.27E−32 A96 Rgn Lcat2 9.19E−37 0.261581087 0.886 0.786 2.28E−32 A96 Lcat Hpgd1 1.45E−36 0.341178641 0.588 0.41 3.59E−32 A96 Hpgd Hmgcs11 1.88E−36 0.325148716 0.858 0.718 4.67E−32 A96 Hmgcs1 Rdh16 2.69E−36 0.347667254 0.494 0.31 6.69E−32 A96 Rdh16 Cyp2c372 2.78E−36 0.414355767 0.71 0.521 6.89E−32 A96 Cyp2c37 Tob11 1.03E−35 0.295824005 0.649 0.487 2.55E−31 A96 Tobi Kif1b 2.07E−35 0.296097725 0.686 0.507 5.15E−31 A96 Kif1b Bnip33 3.84E−35 0.320840361 0.716 0.558 9.53E−31 A96 Bnip3 Ndufa31 4.91E−35 0.274293228 0.737 0.598 1.22E−30 A96 Ndufa3 Apoc22 5.09E−35 0.278106979 0.901 0.815 1.26E−30 A96 Apoc2 Aldh9a11 7.77E−35 0.258476419 0.884 0.786 1.93E−30 A96 Aldh9a1 Cpt1a1 4.44E−34 0.262562089 0.837 0.693 1.10E−29 A96 Cpt1a Hsd17b7 7.40E−34 0.30278955 0.56 0.386 1.84E−29 A96 Hsd17b7 Acat12 7.72E−34 0.255795606 0.917 0.852 1.92E−29 A96 Acat1 D4Wsu53e 8.98E−34 0.292811118 0.597 0.413 2.23E−29 A96 D4Wsu53e Cox5a2 9.78E−34 0.272834577 0.813 0.715 2.43E−29 A96 Cox5a Gsta21 1.28E−33 0.31098189 0.522 0.356 3.17E−29 A96 Gsta2 Cxcl121 1.54E−33 0.28214551 0.635 0.48 3.82E−29 A96 Cxcl12 Baat1 1.66E−33 0.272783991 0.862 0.769 4.13E−29 A96 Baat Cyp2c681 1.69E−33 0.293077044 0.695 0.527 4.20E−29 A96 Cyp2c68 Hsd17b103 4.80E−33 0.280202519 0.841 0.702 1.19E−28 A96 Hsd17b10 Ndufa72 7.78E−33 0.260000131 0.818 0.695 1.93E−28 A96 Ndufa7 Rdx2 1.06E−32 0.256615237 0.824 0.683 2.63E−28 A96 Rdx Gas51 1.39E−32 0.282282316 0.68 0.525 3.46E−28 A96 Gas5 G6pc1 2.86E−32 0.254149322 0.86 0.728 7.09E−28 A96 G6pc Cpeb4 3.54E−32 0.301102867 0.527 0.357 8.79E−28 A96 Cpeb4 Tgoln11 3.58E−32 0.280892109 0.756 0.626 8.89E−28 A96 Tgoln1 Tmed51 4.26E−32 0.252317476 0.714 0.569 1.06E−27 A96 Tmed5 Por3 4.35E−32 0.286727601 0.858 0.701 1.08E−27 A96 Por Abcc31 9.20E−32 0.274329395 0.733 0.572 2.28E−27 A96 Abcc3 Etfdh 9.29E−32 0.263880086 0.811 0.706 2.31E−27 A96 Etfdh Arl4a 1.24E−31 0.270622637 0.517 0.342 3.09E−27 A96 Arl4a Cpox 1.57E−31 0.322921483 0.634 0.486 3.91E−27 A96 Cpox Zfp36l1 2.69E−31 0.296352274 0.601 0.447 6.69E−27 A96 Zfp36l1 Dhdh1 2.78E−31 0.26256299 0.734 0.615 6.90E−27 A96 Dhdh Slco1a41 5.51E−31 0.304909008 0.507 0.336 1.37E−26 A96 Slco1a4 Cyp2c442 1.06E−30 0.273539159 0.828 0.71 2.64E−26 A96 Cyp2c44 Ctage51 1.29E−29 0.253519236 0.837 0.716 3.22E−25 A96 Ctage5 Mia31 2.42E−29 0.260448824 0.81 0.659 6.02E−25 A96 Mia3 Slc25a201 3.50E−29 0.25073463 0.671 0.543 8.69E−25 A96 Slc25a20 G0s22 7.31E−29 0.265563376 0.525 0.35 1.81E−24 A96 G0s2 Oat2 9.25E−29 0.490397584 0.653 0.478 2.30E−24 A96 Oat F5 5.35E−28 0.256577637 0.858 0.754 1.33E−23 A96 F5 Cox8a3 1.48E−27 0.251853134 0.737 0.626 3.67E−23 A96 Cox8a Gm49521 2.35E−27 0.258080982 0.663 0.536 5.82E−23 A96 Gm4952 Pxmp4 1.07E−26 0.255478862 0.687 0.556 2.65E−22 A96 Pxmp4 Ppp1r3b1 1.27E−26 0.250974794 0.536 0.377 3.16E−22 A96 Ppp1r3b Fmo1 3.23E−26 0.264953339 0.606 0.446 8.01E−22 A96 Fmo1 Zfp911 9.57E−26 0.277539527 0.693 0.56 2.38E−21 A96 Zfp91 Apol7a1 3.42E−23 0.25175601 0.559 0.42 8.50E−19 A96 Apo17a Ces1e 5.02E−22 0.256602575 0.71 0.608 1.25E−17 A96 Ces1e Gadd45b 5.16E−21 0.259769736 0.452 0.311 1.28E−16 A96 Gadd45b Etnppl3 6.58E−13 0.315432141 0.677 0.619 1.63E−08 A96 Etnppl Mup174 0 2.016622219 1 0.947 0 UT Mup17 Mup94 0 1.914490248 0.976 0.594 0 UT Mup9 Mup64 0 1.881843585 0.992 0.804 0 UT Mup6 Mup194 0 1.785867292 1 0.916 0 UT Mup19 Mup115 0 1.728428444 1 0.84 0 UT Mup11 Mup184 0 1.638566323 0.997 0.838 0 UT Mup18 Mup54 0 1.341986627 0.839 0.541 0 UT Mup5 Mup154 0 1.259561807 0.617 0.166 0 UT Mup15 Mup164 0 1.12499966 0.934 0.594 0 UT Mup16 mt-Nd44 0 1.115678214 0.998 0.942 0 UT mt-Nd4 mt-Co24 0 1.077728564 0.629 0.157 0 UT mt-Co2 Gm137754 0 1.061267629 0.761 0.306 0 UT Gm13775 mt-Co14 0 0.921896864 0.999 0.977 0 UT mt-Co1 mt-Cytb3 0 0.877546618 0.999 0.971 0 UT mt-Cytb Mup214 0 0.872348794 0.929 0.702 0 UT Mup21 mt-Nd23 0 0.832515437 0.999 0.978 0 UT mt-Nd2 Selenbp23 0 0.830430695 0.937 0.751 0 UT Selenbp2 mt-Nd54 0 0.779679711 0.995 0.942 0 UT mt-Nd5 mt-Nd13 0 0.759986171 1 0.978 0 UT mt-Nd1 mt-Rnr22 0 0.545826779 1 1 0 UT mt-Rnr2 Mup32 0 0.542484173 1 0.999 0 UT Mup3 mt-Co34  1.54E−290 0.958403256 0.603 0.198  3.82E−286 UT mt-Co3 Serpina1e1  1.35E−287 0.468116476 0.999 0.99  3.36E−283 UT Serpina1e Akr1c62  4.68E−230 0.504664681 0.971 0.92  1.16E−225 UT Akr1c6 Ankrd554  6.63E−225 1.230858809 0.696 0.451  1.65E−220 UT Ankrd55 Mup43  8.62E−211 1.000765415 0.898 0.716  2.14E−206 UT Mup4 mt-Rnr13  1.37E−205 0.353829755 1 1  3.40E−201 UT mt-Rnr1 Fabp11  3.44E−187 0.30775699 1 0.992  8.54E−183 UT Fabp1 Elovl33  5.11E−177 0.522135473 0.827 0.65  1.27E−172 UT Elovl3 Gsta32  4.62E−168 0.404911812 0.956 0.958  1.15E−163 UT Gsta3 Mup74  2.96E−167 0.601531682 0.998 0.937  7.35E−163 UT Mup7 Nudt74  3.51E−163 0.6192372 0.83 0.691  8.71E−159 UT Nudt7 Serpina1a1  1.94E−157 0.33473551 0.991 0.96  4.81E−153 UT Serpina1a Uqcrq2  7.40E−157 0.410137125 0.951 0.902  1.84E−152 UT Uqcrq Car32  2.61E−147 0.376245944 0.974 0.956  6.47E−143 UT Car3 Ces3a2  1.36E−137 0.317352764 0.967 0.93  3.38E−133 UT Ces3a Mup84  1.52E−136 0.726763962 0.373 0.13  3.77E−132 UT Mup8 Adh11  1.12E−132 0.31221001 0.96 0.941  2.79E−128 UT Adh1 Prdx12  2.41E−131 0.349862194 0.927 0.878  5.99E−127 UT Prdx1 Gstp12  4.61E−130 0.608807368 0.822 0.702  1.14E−125 UT Gstp1 Hsd3b72  3.94E−128 0.450130172 0.798 0.693  9.79E−124 UT Hsd3b7 Acaa1b3  1.79E−119 0.315795941 0.969 0.883  4.44E−115 UT Acaa1b Mup201  2.74E−117 0.372499315 1 0.992  6.81E−113 UT Mup20 Mup133  3.18E−117 0.624965563 0.546 0.351  7.90E−113 UT Mup13 Rps142  1.62E−111 0.336423845 0.917 0.856  4.03E−107 UT Rsp14 Cyb52  5.75E−109 0.284450423 0.983 0.972  1.43E−104 UT Cyb5 2810007J24Rik1  3.82E−107 0.287090402 0.943 0.909  9.49E−103 UT 2810007J24Rik Hsd3b54  2.16E−104 0.471194244 0.587 0.367  5.37E−100 UT Hsd3b5 Mup124  3.61E−104 0.371327569 0.86 0.665  8.97E−100 UT Mup12 Cox4i12 2.61E−94 0.262749367 0.958 0.941 6.48E−90 UT Cox4i1 Oaz11 5.51E−93 0.394430119 0.75 0.651 1.37E−88 UT Oaz1 Tmem2052 1.10E−91 0.295263774 0.934 0.877 2.74E−87 UT Tmem205 Serpina3c3 4.51E−84 0.425256202 0.385 0.208 1.12E−79 UT Serpina3c Ugt2b11 1.86E−83 0.30063164 0.871 0.817 4.62E−79 UT Ugt2b1 Rps23 3.51E−80 0.379370911 0.757 0.637 8.73E−76 UT Rps2 Inmt2 1.03E−77 0.366227618 0.884 0.871 2.55E−73 UT Inmt Cox6c2 1.98E−73 0.343178548 0.884 0.808 4.92E−69 UT Cox6c Ndufb112 7.98E−73 0.352187855 0.735 0.637 1.98E−68 UT Ndufb11 Cyp7b13 1.18E−72 0.351246722 0.757 0.654 2.92E−68 UT Cyp7b1 Cyp1a22 2.21E−72 0.303458132 0.794 0.621 5.49E−68 UT Cyp1a2 C8g2 9.19E−72 0.258246671 0.91 0.859 2.28E−67 UT C8g Lifr3 5.26E−70 0.353193545 0.694 0.608 1.31E−65 UT Lifr Hamp3 1.12E−69 0.274177459 0.884 0.718 2.79E−65 UT Hamp Cfhr21 1.47E−66 0.329112182 0.868 0.854 3.64E−62 UT Cfhr2 Mup143 2.61E−61 0.524421073 0.616 0.469 6.49E−57 UT Mup14 Aadac2 2.88E−59 0.324280061 0.86 0.849 7.15E−55 UT Aadac Keg13 4.07E−58 0.385687903 0.545 0.441 1.01E−53 UT Keg1 Cyp2a52 7.24E−58 0.327337224 0.555 0.388 1.80E−53 UT Cyp2a5 Chchd22 3.96E−57 0.257495549 0.916 0.874 9.83E−53 UT Chchd2 Ces3b1 1.20E−56 0.283988668 0.787 0.727 2.98E−52 UT Ces3b Ttc39c2 4.98E−56 0.318694789 0.642 0.573 1.24E−51 UT Ttc39c Gstm32 2.30E−53 0.47361305 0.414 0.269 5.70E−49 UT Gstm3 Gadd45g1 9.92E−53 0.340515267 0.639 0.503 2.46E−48 UT Gadd45g Ndufa42 7.60E−52 0.261719376 0.889 0.851 1.89E−47 UT Ndufa4 Cml11 7.90E−52 0.295319392 0.757 0.709 1.96E−47 UT Cml1 Thrsp3 3.45E−50 0.460250446 0.627 0.583 8.56E−46 UT Thrsp mt-Atp62 2.06E−48 0.419380785 0.452 0.311 5.11E−44 UT mt-Atp6 Rpl321 1.00E−47 0.30384302 0.757 0.688 2.49E−43 UT Rpl32 Hspe11 2.75E−44 0.308522832 0.557 0.462 6.83E−40 UT Hspe1 Hsd3b31 2.62E−41 0.282851137 0.605 0.519 6.51E−37 UT Hsd3b3 Serpina122 6.83E−41 0.279022117 0.492 0.362 1.70E−36 UT Serpina12 Prdx41 1.19E−38 0.290503348 0.607 0.55 2.95E−34 UT Prdx4 Mup24 3.60E−37 0.446904247 0.392 0.285 8.95E−33 UT Mup2 Cox7a22 2.72E−36 0.251096024 0.784 0.722 6.76E−32 UT Cox7a2 Cyp2b102 2.41E−35 0.502782767 0.542 0.493 5.98E−31 UT Cyp2b10 Ndufs62 3.36E−32 0.272052906 0.724 0.678 8.33E−28 UT Ndufs6 Ndufb41 1.61E−29 0.253090085 0.49 0.409 3.99E−25 UT Ndufb4 Rpl36al1 8.10E−27 0.2702077 0.551 0.495 2.01E−22 UT Rpl36al Mup116 1.57E−24 0.470008649 0.583 0.522 3.91E−20 UT Mup1 Rps152 4.98E−19 0.272193403 0.528 0.49 1.24E−14 UT Rps15 Ubb 5.31E−19 0.264147083 0.45 0.394 1.32E−14 UT Ubb Ftl1 2.27E−15 0.309991928 0.409 0.367 5.64E−11 UT Ftl1

Surprisingly, Applicants noticed many of the response genes have very similar patterns of upregulation in both injury models, including upregulation of genes related to damage response, redox, liver function (Alb) and pathway enrichments shared between APAP and PH as shown in Table 11. Upregulation of anti-oxidative stress genes unsurprisingly follows APAP exposure, in which involvement of ROS is a major cause of injury. However, upregulation of select anti-oxidative stress genes within the PH model, which does not involve a component of oxidative stress, suggests these and other shared genes may participate in a general insult-response module, which is activated in response to many types of damage. Pathway enrichments unique to APAP are provided in Table 9, Pathway enrichments unique to PH, in Table 10.

TABLE 9 Pathway enrichments unique to APAP. Genes. Stat.non. p.non. padj.non. Genes. Stat.mix. p.mix. padj.mix. Genes. Stat.mix. p.mix. padj.mix. tot._(—) dir.._(—) dir.._(—) dir.._(—) up._(—) dir.up._(—) dir.up._(—) dir.up._(—) down._(—) dir.dn._(—) dir.dn._(—) dir.dn._(—) APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP KEGG_PPAR_SIGNALING_PATHWAY 22 7823.4 0.00 0.02 9 3462.1 0.00 0.04 13 4361.3 0.00 0.57 KEGG_COMPLEMENT_AND_COAGULATION_CASCADES 26 8046.9 0.00 0.06 20 6277.6 0.01 0.10 6 1769.3 0.11 1.00 REACTOME_PPARA_ACTIVATES_GENE_EXPRESSION 23 7289.1 0.00 0.06 17 5546.6 0.01 0.09 6 1742.5 0.12 1.00 REACTOME_BIOLOGICAL_OXIDATIONS 30 9098.2 0.00 0.06 12 3471.3 0.10 0.45 18 5627 0.00 0.57 REACTOME_METABOLISM_OF_LIPIDS_AND_LIPOPROTEINS 101 28033 0.00 0.04 67 20622 0.00 0.01 34 7410.2 0.39 1.00 SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN 23 7693.5 0.00 0.04 15 5172.6 0.00 0.05 8 2520.9 0.03 0.94 TIEN_INTESTINE_PROBIOTICS_24 HR_DN 62 17374 0.00 0.06 47 14200 0.00 0.03 15 3174.2 0.48 1.00 TARTE_PLASMA_CELL_VS_PLASMABLAST_UP 46 13841 0.00 0.04 25 7761 0.01 0.08 21 6079.9 0.01 0.69 LEE_LIVER_CANCER_DENA_DN 36 10808 0.00 0.04 7 2520 0.02 0.16 29 8288.4 0.00 0.69 HSIAO_LIVER_SPECIFIC_GENES 131 42605 0.00 0.02 73 26630 0.00 0.01 58 15975 0.00 0.39 MUNSHI_MULTIPLE_MYELOMA_UP 20 6523.9 0.00 0.06 12 4427.7 0.00 0.03 8 2096.2 0.18 1.00 TAKAO_RESPONSE_TO_UVB_RADIATION_UP 26 7896.4 0.00 0.09 8 2743.9 0.02 0.18 18 5152.5 0.02 0.82 KAAB_HEART_ATRIUM_VS_VENTRICLE_UP 22 6839.7 0.00 0.09 15 5295.8 0.00 0.04 7 1543.9 0.43 1.00 RODWELL_AGING_KIDNEY_NO_BLOOD_UP 25 7724.8 0.00 0.06 19 6355.2 0.00 0.04 6 1369.6 0.38 1.00 CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 91 23927 0.00 0.10 74 19930 0.01 0.12 17 3997.3 0.25 1.00 ACEVEDO_LIVER_CANCER_DN 138 39248 0.00 0.02 80 26286 0.00 0.01 58 12962 0.25 1.00 SMID_BREAST_CANCER_BASAL_DN 82 22484 0.00 0.04 50 14455 0.00 0.06 32 8028.5 0.07 1.00 BOCHKIS_FOXA2_TARGETS 106 27826 0.00 0.08 63 16811 0.03 0.22 43 11015 0.02 0.85 BOQUEST_STEM_CELL_UP 26 8561.2 0.00 0.04 16 5723 0.00 0.03 10 2838.2 0.08 1.00 SWEET_LUNG_CANCER_KRAS_DN 55 15677 0.00 0.06 36 10466 0.01 0.10 19 5211.5 0.04 0.94 ZHANG_TLX_TARGETS_60 HR_UP 32 9533.3 0.00 0.09 23 7214.3 0.01 0.08 9 2318.9 0.18 1.00 BOYAULT_LIVER_CANCER_SUBCLASS_G123_DN 23 7152.8 0.00 0.08 13 4470.2 0.00 0.07 10 2682.6 0.13 1.00 CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_DN 77 20983 0.00 0.06 33 11045 0.00 0.01 44 9938 0.25 1.00 YAMASHITA_LIVER_CANCER_STEM_CELL_DN 33 10027 0.00 0.06 17 5107.1 0.03 0.27 16 4919.9 0.01 0.69 WOO_LIVER_CANCER_RECURRENCE_DN 38 11695 0.00 0.03 17 5508.3 0.01 0.10 21 6186.7 0.01 0.69 HOSHIDA_LIVER_CANCER_SUBCLASS_S3 111 30365 0.00 0.04 54 17777 0.00 0.01 57 12588 0.29 1.00 CAIRO_HEPATOBLASTOMA_DN 102 27531 0.00 0.04 53 16333 0.00 0.03 49 11198 0.20 1.00 CAIRO_HEPATOBLASTOMA_CLASSES_DN 45 12828 0.00 0.09 26 7144.5 0.07 0.38 19 5683.9 0.01 0.69 CAIRO_LIVER_DEVELOPMENT_DN 100 28189 0.00 0.03 63 20717 0.00 0.01 37 7471.8 0.64 1.00 SERVITJA_LIVER_HNF1A_TARGETS_UP 20 6447.4 0.00 0.06 15 4903.8 0.01 0.11 5 1543.6 0.09 1.00 NABA_MATRISOME 69 20317 0.00 0.02 59 18644 0.00 0.01 10 1673.9 0.81 1.00 VILLANUEVA_LIVER_CANCER_KRT19_DN 24 7562.1 0.00 0.06 11 4125.1 0.00 0.04 13 3437 0.11 1.00 GO_FATTY_ACID_CATABOLIC_PROCESS 28 8095 0.01 0.08 15 5348.5 0.00 0.01 13 2746.5 0.48 0.98 GO_AMMONIUM_ION_METABOLIC_PROCESS 34 11097 0.00 0.01 21 7993.5 0.00 0.00 13 3103.2 0.26 0.83 GO_PROTEIN_ACTIVATION_CASCADE 26 8061.5 0.00 0.03 20 6309.4 0.01 0.04 6 1752.1 0.10 0.64 GO_REGULATION_OF_WOUND_HEALING 21 6945.8 0.00 0.01 18 6360.3 0.00 0.01 3 585.59 0.56 1.00 GO_RESPONSE_TO_ESTRADIOL 24 7016.7 0.02 0.09 17 5334.2 0.01 0.07 7 1682.5 0.30 0.86 GO_RESPONSE_TO_ACID_CHEMICAL 57 15642 0.00 0.04 37 10651 0.01 0.06 20 4991.6 0.13 0.66 GO_STEROL_HOMEOSTASIS 21 6247.9 0.02 0.09 11 3538.4 0.03 0.12 10 2709.5 0.11 0.64 GO_LIPOPROTEIN_METABOLIC_PROCESS 20 6956.1 0.00 0.01 14 4569.3 0.01 0.06 6 2386.8 0.00 0.26 GO_FATTY_ACID_BETA_OXIDATION 22 6503.2 0.01 0.09 12 4501.3 0.00 0.01 10 2001.9 0.57 1.00 GO_PROTEIN_MATURATION 32 9466.7 0.00 0.03 23 7517.9 0.00 0.02 9 1948.8 0.44 0.96 GO_POSITIVE_REGULATION_OF_LOCOMOTION 38 10715 0.01 0.07 33 9976.1 0.00 0.03 5 739.16 0.81 1.00 GO_ORGANIC_HYDROXY_COMPOUND_METABOLIC_PROCESS 113 30659 0.00 0.01 61 19192 0.00 0.00 52 11468 0.31 0.88 GO_ORGANIC_ACID_BIOSYNTHETIC_PROCESS 69 18105 0.01 0.09 30 9094.8 0.00 0.04 39 9010 0.19 0.74 GO_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS 115 30536 0.00 0.01 55 17539 0.00 0.00 60 12996 0.37 0.91 GO_RESPONSE_TO_INORGANIC_SUBSTANCE 88 22912 0.01 0.06 59 15860 0.02 0.11 29 7052.4 0.12 0.66 GO_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT 34 11187 0.00 0.01 28 9240.7 0.00 0.01 6 1946.2 0.04 0.55 GO_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS 21 7538.8 0.00 0.00 14 5374.9 0.00 0.00 7 2163.9 0.06 0.56 GO_ORGANIC_HYDROXY_COMPOUND_TRANSPORT 31 9865.3 0.00 0.01 18 6306 0.00 0.01 13 3559.2 0.07 0.56 GO_DEFENSE_RESPONSE 121 32545 0.00 0.01 89 23374 0.02 0.09 32 9171.1 0.00 0.26 GO_ORGANOPHOSPHATE_ESTER_TRANSPORT 20 6642 0.00 0.01 13 3866.1 0.06 0.22 7 2775.9 0.00 0.26 GO_LIPID_HOMEOSTASIS 35 10260 0.00 0.03 21 6598.3 0.01 0.05 14 3661.5 0.11 0.64 GO_SECRETION 58 17186 0.00 0.00 48 15502 0.00 0.00 10 1684 0.80 1.00 GO_ANION_TRANSPORT 59 15946 0.01 0.06 38 11431 0.00 0.03 21 4515.4 0.44 0.95 GO_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS 34 10760 0.00 0.01 23 7092.6 0.01 0.05 11 3667.3 0.01 0.35 GO_RESPONSE_TO_XENOBIOTIC_STIMULUS 21 6511 0.01 0.05 6 2131.7 0.02 0.12 15 4379.4 0.02 0.44 GO_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_(—) 30 9595.6 0.00 0.01 26 8757.6 0.00 0.01 4 837.98 0.48 0.98 STIMULUS GO_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS 106 28989 0.00 0.01 52 17188 0.00 0.00 54 11801 0.33 0.90 GO_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS 89 25237 0.00 0.00 69 19702 0.00 0.01 20 5534.6 0.03 0.52 GO_REGULATION_OF_LIPID_METABOLIC_PROCESS 56 17326 0.00 0.00 34 10855 0.00 0.01 22 6471.7 0.01 0.35 GO_AMINE_METABOLIC_PROCESS 32 10016 0.00 0.01 17 6153.3 0.00 0.00 15 3862.4 0.13 0.66 GO_AUTOPHAGY 35 9748.3 0.02 0.10 26 7361.8 0.04 0.15 9 2386.5 0.15 0.70 GO_REGULATION_OF_SECRETION 56 15716 0.00 0.03 47 13424 0.01 0.04 9 2292.3 0.20 0.75 GO_APOPTOTIC_SIGNALING_PATHWAY 34 9850.6 0.01 0.05 26 7310 0.04 0.17 8 2540.6 0.03 0.50 GO_ACUTE_INFLAMMATORY_RESPONSE 25 8681.7 0.00 0.01 18 6505.8 0.00 0.00 7 2175.9 0.05 0.56 GO_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS 61 17142 0.00 0.02 42 12406 0.00 0.03 19 4736.1 0.14 0.68 GO_MAINTENANCE_OF_LOCATION 22 7094.1 0.00 0.02 18 6373.1 0.00 0.01 4 721.06 0.62 1.00 GO_POSITIVE_REGULATION_OF_PROTEIN_SECRETION 21 6254.7 0.01 0.09 18 5654.2 0.01 0.06 3 600.47 0.53 1.00 GO_ORGANIC_ACID_METABOLIC_PROCESS 202 51076 0.00 0.02 100 29277 0.00 0.00 102 21799 0.40 0.94 GO_RESPONSE_TO_OXYGEN_LEVELS 35 9850.8 0.01 0.08 25 7215.4 0.03 0.12 10 2635.4 0.14 0.68 GO_REGULATION_OF_CELLULAR_KETONE_METABOLIC_PROCESS 37 10386 0.01 0.07 18 6076.1 0.00 0.02 19 4309.7 0.32 0.89 GO_ORGANIC_ACID_CATABOLIC_PROCESS 74 19313 0.01 0.09 32 10483 0.00 0.01 42 8830.5 0.49 0.98 GO_REGULATION_OF_RESPONSE_TO_WOUNDING 57 17902 0.00 0.00 45 14043 0.00 0.00 12 3858.7 0.01 0.38 GO_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_(—) 23 7361 0.00 0.01 20 6215.2 0.01 0.06 3 1145.7 0.04 0.53 PATHWAY GO_CELLULAR_LIPID_CATABOLIC_PROCESS 42 13000 0.00 0.01 23 8176.2 0.00 0.00 19 4824.1 0.11 0.65 GO_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_(—) 23 6763.4 0.01 0.09 13 4359.2 0.01 0.05 10 2404.1 0.27 0.83 PROCESS GO_DETOXIFICATION 23 7116.3 0.00 0.03 9 2877.1 0.04 0.17 14 4239.1 0.02 0.40 GO_REGULATION_OF_PEPTIDASE_ACTIVITY 53 14643 0.01 0.05 36 11427 0.00 0.01 17 3216.6 0.71 1.00 GO_ORGANIC_ANION_TRANSPORT 54 15332 0.00 0.02 35 11024 0.00 0.01 19 4308.2 0.32 0.89 GO_INFLAMMATORY_RESPONSE 58 17317 0.00 0.00 43 13110 0.00 0.01 15 4206.7 0.05 0.55 GO_NEGATIVE_REGULATION_OF_CELL_DEATH 107 28526 0.00 0.01 85 22340 0.02 0.11 22 6185.4 0.02 0.40 GO_FATTY_ACID_METABOLIC_PROCESS 69 19656 0.00 0.01 40 13112 0.00 0.00 29 6544.5 0.28 0.84 GO_LIPID_METABOLIC_PROCESS 196 52216 0.00 0.01 113 33135 0.00 0.00 83 19081 0.11 0.64 GO_DIVALENT_INORGANIC_CATION_HOMEOSTASIS 25 7615.9 0.00 0.04 19 5393.1 0.06 0.22 6 2222.8 0.01 0.35 GO_REGULATION_OF_ENDOCYTOSIS 20 6706.3 0.00 0.01 15 4807.9 0.01 0.07 5 1898.5 0.01 0.38 GO_ALCOHOL_METABOLIC_PROCESS 81 21911 0.00 0.03 44 13202 0.00 0.01 37 8709 0.15 0.71 GO_IMMUNE_RESPONSE 86 22263 0.01 0.09 63 15638 0.16 0.41 23 6624.3 0.01 0.38 GO_CELLULAR_LIPID_METABOLIC_PROCESS 148 40329 0.00 0.00 88 26491 0.00 0.00 60 13838 0.14 0.68 GO_MONOCARBOXYLIC_ACID_TRANSPORT 28 8200.8 0.01 0.06 18 6208.2 0.00 0.01 10 1992.7 0.58 1.00 GO_NEGATIVE_REGULATION_OF_APOPTOTIC_SIGNALING_(—) 30 9140.9 0.00 0.02 24 7115.5 0.02 0.09 6 2025.3 0.03 0.50 PATHWAY GO_MULTICELLULAR_ORGANISMAL_HOMEOSTASIS 26 8484.4 0.00 0.01 20 6159.3 0.01 0.07 6 2325.1 0.00 0.26 GO_ORGANIC_HYDROXY_COMPOUND_BIOSYNTHETIC_PROCESS 48 13228 0.01 0.06 24 8180.2 0.00 0.01 24 5047.9 0.50 0.98 GO_REGULATION_OF_CELL_DEATH 159 40571 0.00 0.03 126 32290 0.02 0.09 33 8281.4 0.07 0.56 GO_LIPID_CATABOLIC_PROCESS 54 15902 0.00 0.01 31 10400 0.00 0.00 23 5502.7 0.19 0.74 GO_POSITIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS 30 11217 0.00 0.00 21 7735.3 0.00 0.01 9 3481.6 0.00 0.26 GO_REGULATION_OF_STEROID_METABOLIC_PROCESS 25 7971.2 0.00 0.01 14 4365 0.02 0.11 11 3606.2 0.01 0.38 GO_REGULATION_OF_INFLAMMATORY_RESPONSE 41 13291 0.00 0.00 30 9480.9 0.00 0.02 11 3809.6 0.00 0.26 GO_RESPONSE_TO_TOXIC_SUBSTANCE 48 13391 0.01 0.04 23 6552.7 0.04 0.17 25 6838.1 0.02 0.42 GO_CELLULAR_CHEMICAL_HOMEOSTASIS 62 17171 0.00 0.02 42 12277 0.01 0.04 20 4894.2 0.16 0.71 GO_POSITIVE_REGULATION_OF_TRANSPORT 86 22281 0.01 0.09 64 16810 0.04 0.16 22 5471.6 0.12 0.66 GO_REGULATION_OF_LIPID_CATABOLIC_PROCESS 21 7420.9 0.00 0.00 12 4869.3 0.00 0.00 9 2551.6 0.09 0.59 GO_REGULATION_OF_IMMUNE_EFFECTOR_PROCESS 36 10243 0.01 0.07 24 6890.9 0.04 0.15 12 3351.6 0.07 0.56 GO_LIPID_LOCALIZATION 61 17939 0.00 0.00 41 13294 0.00 0.00 20 4644.4 0.26 0.83 GO_REGULATION_OF_PROTEOLYSIS 93 23839 0.01 0.09 61 17051 0.00 0.03 32 6788.6 0.47 0.97 GO_POSITIVE_REGULATION_OF_SECRETION 30 9267.7 0.00 0.01 26 8328.8 0.00 0.02 4 938.94 0.37 0.91 GO_NEGATIVE_REGULATION_OF_RESPONSE_TO_WOUNDING 27 8785.1 0.00 0.01 21 6818 0.00 0.03 6 1967.1 0.04 0.53 GO_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_(—) 90 23438 0.01 0.06 64 16486 0.07 0.23 26 6951.7 0.03 0.52 PROCESS GO_CELLULAR_HOMEOSTASIS 79 21946 0.00 0.01 54 15425 0.00 0.03 25 6521.7 0.05 0.56 GO_SINGLE_ORGANISM_CATABOLIC_PROCESS 166 42191 0.00 0.03 83 23989 0.00 0.00 83 18202 0.28 0.84 GO_RESPONSE_TO_OXIDATIVE_STRESS 61 16457 0.01 0.06 39 10687 0.03 0.13 22 5770.5 0.06 0.56 GO_BEHAVIOR 31 8972 0.01 0.06 21 6660.3 0.01 0.04 10 2311.7 0.33 0.90 GO_ACUTE_PHASE_RESPONSE 21 7319.5 0.00 0.01 15 5604.1 0.00 0.00 6 1715.4 0.12 0.66 GO_NEGATIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_(—) 35 9962.4 0.01 0.07 27 7899.4 0.02 0.09 8 2063 0.20 0.75 STIMULUS GO_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY 54 15199 0.00 0.02 43 12306 0.01 0.04 11 2892.7 0.14 0.68 GO_NEGATIVE_REGULATION_OF_CELL_PROLIFERATION 48 14057 0.00 0.01 34 10182 0.00 0.03 14 3875.5 0.06 0.56 GO_RESPONSE_TO_REACTIVE_OXYGEN_SPECIES 36 10248 0.01 0.07 23 6148.8 0.12 0.34 13 4099.2 0.01 0.38 GO_ENDOCYTIC_VESICLE 25 7350.4 0.01 0.08 19 5246.5 0.09 0.29 6 2103.9 0.02 0.40 GO_ENDOPLASMIC_RETICULUM_PART 168 42254 0.00 0.04 119 31832 0.00 0.02 49 10422 0.46 0.97 GO_ENDOPLASMIC_RETICULUM_LUMEN 36 10132 0.01 0.09 28 8391.3 0.01 0.05 8 1740.3 0.44 0.95 GO_ENDOPLASMIC_RETICULUM 214 53290 0.00 0.03 152 39291 0.01 0.04 62 13999 0.21 0.75 GO_LIPID_TRANSPORTER_ACTIVITY 27 9133.9 0.00 0.00 17 6244.4 0.00 0.00 10 2889.5 0.06 0.56 GO_SULFUR_COMPOUND_BINDING 36 12559 0.00 0.00 23 8121.4 0.00 0.00 13 4437.8 0.00 0.26 GO_STEROID_BINDING 20 6566.6 0.00 0.01 10 3560.3 0.01 0.04 10 3006.3 0.04 0.53 GO_GLYCOSAMINOGLYCAN_BINDING 20 6655.2 0.00 0.01 17 5696.2 0.00 0.03 3 959.02 0.14 0.68 GO_ALCOHOL_BINDING 20 7130.5 0.00 0.01 10 3920.7 0.00 0.01 10 3209.7 0.01 0.40 GO_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY 21 6241.5 0.02 0.10 12 4474.4 0.00 0.01 9 1767.1 0.60 1.00 GO_LIPID_BINDING 81 21990 0.00 0.03 53 14919 0.01 0.04 28 7070.2 0.07 0.56 GO_RECEPTOR_BINDING 144 38089 0.00 0.00 105 28493 0.00 0.02 39 9595.4 0.07 0.56 GO_COENZYME_BINDING 46 13083 0.00 0.03 27 8640.9 0.00 0.02 19 4442.1 0.26 0.83 HALLMARK_ADIPOGENESIS 66 18461 0.00 0.01 35 11301 0.00 0.00 31 7160 0.22 0.80 HALLMARK_XENOBIOTIC_METABOLISM 79 25124 0.00 0.00 45 16165 0.00 0.00 34 8958.6 0.02 0.58 HALLMARK_FATTY_ACID_METABOLISM 56 14864 0.02 0.06 29 9719.9 0.00 0.00 27 5144.5 0.75 0.99 HALLMARK_COAGULATION 44 12802 0.00 0.01 32 9497 0.01 0.02 12 3304.8 0.08 0.80 HALLMARK_BILE_ACID_METABOLISM 47 13258 0.00 0.02 21 7236 0.00 0.00 26 6022.1 0.24 0.80 HALLMARK_PEROXISOME 38 10985 0.01 0.03 20 6649.6 0.00 0.01 18 4335.2 0.20 0.80

TABLE 10 Pathway enrichments unique to PH. Genes. Stat.non. p.non. padj.non. Genes. Stat.mix. p.mix. padj.mix. Genes. Stat.mix. p.mix. padj.mix. tot._(—) dir.._(—) dir.._(—) dir.._(—) up._(—) dir.up._(—) dir.up._(—) dir.up._(—) down._(—) dir.dn._(—) dir.dn._(—) dir.dn._(—) APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP SENESE_HDAC3_TARGETS_UP 75 13473 0.99 1.00 70 12747 1.00 1.00 5 725.8 0.82 1.00 BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_UP 102 21480 0.77 1.00 90 18877 0.90 1.00 12 2603.8 0.42 1.00 GERY_CEBP_TARGETS 28 7584.2 0.05 0.38 22 6232.4 0.05 0.33 6 1351.8 0.40 1.00 FOSTER_TOLERANT_MACROPHAGE_DN 48 10226 0.65 1.00 45 9539.9 0.77 1.00 3 686.22 0.39 1.00 BLUM_RESPONSE_TO_SALIRASIB_UP 53 12422 0.28 0.86 50 11521 0.47 0.99 3 901.04 0.18 1.00 WONG_ADULT_TISSUE_STEM_MODULE 83 19476 0.22 0.79 63 14741 0.41 0.92 20 4734.8 0.22 1.00 PILON_KLF1_TARGETS_UP 93 23146 0.04 0.35 72 19825 0.00 0.07 21 3321 0.94 1.00 GO_ANATOMICAL_STRUCTURE_FORMATION_INVOLVED_IN_(—) 56 13042 0.29 0.66 49 12197 0.19 0.45 7 845.45 0.94 1.00 MORPHOGENESIS GO_CIRCULATORY_SYSTEM_PROCESS 35 9196.8 0.06 0.24 24 6528.3 0.09 0.28 11 2668.5 0.25 0.82 GO_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS 37 9083.2 0.17 0.48 32 7625.3 0.37 0.70 5 1457.8 0.13 0.66 GO_RESPONSE_TO_WOUNDING 69 17868 0.02 0.11 59 15896 0.02 0.11 10 1971.7 0.60 1.00 GO_CELLULAR_RESPONSE_TO_EXTRACELLULAR_STIMULUS 25 6176.3 0.21 0.53 20 4718.4 0.42 0.77 5 1457.8 0.13 0.66 GO_CELL_ACTIVATION 41 9934.8 0.19 0.52 37 8671.2 0.43 0.78 4 1263.6 0.09 0.61 GO_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND 102 21984 0.66 1.00 71 15558 0.72 1.00 31 6426.1 0.53 1.00 GO_VESICLE_MEDIATED_TRANSPORT 129 29919 0.22 0.55 111 26242 0.30 0.61 18 3676.9 0.56 1.00 GO_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY 60 11703 0.91 1.00 50 9424.2 0.97 1.00 10 2278.4 0.36 0.91 GO_RESPONSE_TO_BACTERIUM 54 14413 0.02 0.10 36 9569.4 0.08 0.27 18 4843.7 0.06 0.56 GO_REGULATION_OF_CATABOLIC_PROCESS 91 23179 0.02 0.12 61 16224 0.03 0.13 30 6954.8 0.22 0.80 GO_RESPONSE_TO_KETONE 36 9267.4 0.09 0.31 28 8068.1 0.02 0.11 8 1199.3 0.86 1.00 GO_POSITIVE_REGULATION_OF_CELL_ADHESION 29 7617.2 0.08 0.29 25 6568.2 0.14 0.36 4 1049.1 0.25 0.83 GO_RESPONSE_TO_HORMONE 130 31935 0.03 0.17 92 24993 0.00 0.03 38 6942.1 0.87 1.00 GO_BLOOD_VESSEL_MORPHOGENESIS 35 9233.1 0.06 0.23 29 7973.1 0.06 0.22 6 1260.1 0.49 0.98 GO_RESPONSE_TO_ESTROGEN 31 8617.4 0.02 0.13 21 6012.8 0.05 0.19 10 2604.5 0.16 0.71 GO_RESPONSE_TO_RADIATION 29 5711.7 0.80 1.00 23 4585.5 0.83 1.00 6 1126.1 0.63 1.00 GO_RESPONSE_TO_EXTRACELLULAR_STIMULUS 71 17910 0.05 0.22 44 11428 0.10 0.29 27 6481.9 0.16 0.71 GO_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND 57 11255 0.89 1.00 44 8785.4 0.90 1.00 13 2469.4 0.68 1.00 GO_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY 104 25690 0.04 0.19 77 19130 0.13 0.35 27 6560 0.13 0.67 GO_VASCULATURE_DEVELOPMENT 39 9667.3 0.14 0.42 33 8407.2 0.17 0.43 6 1260.1 0.49 0.98 GO_RESPONSE_TO_ABIOTIC_STIMULUS 93 22945 0.05 0.22 69 17712 0.07 0.24 24 5233.9 0.40 0.94 GO_RESPONSE_TO_DRUG 72 17868 0.07 0.27 43 11067 0.12 0.33 29 6800.6 0.19 0.74 GO_RESPONSE_TO_GROWTH_FACTOR 39 7982.8 0.75 1.00 32 6574.3 0.81 1.00 7 1408.5 0.55 1.00 GO_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS 120 27553 0.27 0.63 90 22010 0.17 0.42 30 5542.5 0.82 1.00 GO_TRANSMEMBRANE_RECEPTOR_PROTEIN_TYROSINE_KINASE_(—) 46 8645.1 0.93 1.00 40 7347.9 0.97 1.00 6 1297.2 0.46 0.97 SIGNALING_PATHWAY GO_CELLULAR_RESPONSE_TO_PEPTIDE 39 7740.3 0.82 1.00 31 6406.6 0.79 1.00 8 1333.8 0.78 1.00 GO_HEXOSE_METABOLIC_PROCESS 23 5891.2 0.15 0.43 11 3367.8 0.05 0.20 12 2523.3 0.48 0.98 GO_CELLULAR_RESPONSE_TO_STRESS 149 32891 0.53 0.97 115 24498 0.88 1.00 34 8393.2 0.08 0.58 GO_ENDOCYTOSIS 55 12969 0.25 0.60 45 10610 0.39 0.74 10 2358.7 0.30 0.86 GO_CIRCULATORY_SYSTEM_DEVELOPMENT 56 12966 0.31 0.69 45 11136 0.22 0.51 11 1830.1 0.83 1.00 GO_RESPONSE_TO_STARVATION 26 6430.6 0.19 0.52 19 5300.9 0.08 0.27 7 1129.7 0.79 1.00 GO_HEMOSTASIS 38 10217 0.03 0.17 33 9397.9 0.02 0.10 5 819.47 0.73 1.00 GO_RESPONSE_TO_MOLECULE_OF_BACTERIAL_ORIGIN 38 9958.5 0.06 0.23 26 6585.1 0.21 0.50 12 3373.4 0.06 0.56 NA NA NA NA NA NA NA NA NA NA NA NA NA GO_CELL_SURFACE 63 15190 0.15 0.45 55 14046 0.10 0.31 8 1143.9 0.89 1.00 GO_PEPTIDASE_REGULATOR_ACTIVITY 32 8831.6 0.02 0.13 24 7480.4 0.01 0.04 8 1351.2 0.76 1.00 NA.1 NA NA NA NA NA NA NA NA NA NA NA NA GO_MOLECULAR_FUNCTION_REGULATOR 109 27456 0.02 0.11 84 20954 0.11 0.32 25 6501.3 0.05 0.56 GO_PEPTIDASE_INHIBITOR_ACTIVITY 24 6956.3 0.02 0.11 19 6368.7 0.00 0.02 5 587.56 0.91 1.00 GO_PHOSPHOLIPID_BINDING 39 9728.5 0.13 0.41 28 6245.1 0.58 0.94 11 3483.4 0.02 0.40 HALLMARK_TNFA_SIGNALING_VIA_NFKB 41 9591.7 0.30 0.43 38 9112.1 0.34 0.48 3 479.62 0.69 0.99 Genes. Stat.non. p.non. padj.non. Genes. Stat.mix. p.mix. padj.mix. Genes. Stat.mix. p.mix. padj.mix. tot._(—) dir.._(—) dir.._(—) dir.._(—) up._(—) dir.up._(—) dir.up._(—) dir.up._(—) down._(—) dir.dn._(—) dir.dn._(—) dir.dn._(—) PH PH PH PH PH PH PH PH PH PH PH PH SENESE_HDAC3_TARGETS_UP 32 13300 0.00 0.06 29 12340 0.00 0.15 3 960.52 0.53 1.00 BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_UP 50 20022 0.00 0.06 44 18582 0.00 0.12 6 1440 0.92 1.00 GERY_CEBP_TARGETS 30 12477 0.00 0.08 27 11455 0.01 0.18 3 1022.1 0.45 1.00 FOSTER_TOLERANT_MACROPHAGE_DN 27 11513 0.00 0.05 25 10728 0.00 0.15 2 785.41 0.27 1.00 BLUM_RESPONSE_TO_SALIRASIB_UP 20 8679.2 0.00 0.06 17 7593.1 0.00 0.14 3 1086.1 0.30 1.00 WONG_ADULT_TISSUE_STEM_MODULE 61 24461 0.00 0.05 51 21066 0.00 0.15 10 3395.8 0.34 1.00 PILON_KLF1_TARGETS_UP 51 20388 0.00 0.08 36 14725 0.02 0.28 15 5662.9 0.05 1.00 GO_ANATOMICAL_STRUCTURE_FORMATION_INVOLVED_IN_(—) 34 13552 0.01 0.06 29 11738 0.06 0.28 5 1813.7 0.26 1.00 MORPHOGENESIS GO_CIRCULATORY_SYSTEM_PROCESS 22 8978.4 0.01 0.08 17 6980.5 0.08 0.34 5 1997.9 0.10 0.80 GO_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS 28 11316 0.01 0.07 24 10140 0.01 0.21 4 1175.3 0.67 1.00 GO_RESPONSE_TO_WOUNDING 51 20277 0.00 0.03 42 17126 0.02 0.21 9 3150.7 0.27 1.00 GO_CELLULAR_RESPONSE_TO_EXTRACELLULAR_STIMULUS 23 9751.4 0.00 0.03 20 8698.6 0.00 0.18 3 1052.7 0.39 1.00 GO_CELL_ACTIVATION 27 11250 0.00 0.03 24 10335 0.00 0.18 3 915.54 0.59 1.00 GO_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND 56 21925 0.00 0.05 41 16778 0.02 0.21 15 5147.1 0.27 1.00 GO_VESICLE_MEDIATED_TRANSPORT 82 31632 0.00 0.04 70 27402 0.07 0.31 12 4230.5 0.22 1.00 GO_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY 32 13199 0.00 0.03 27 11210 0.02 0.21 5 1989.9 0.10 0.80 GO_RESPONSE_TO_BACTERIUM 36 14568 0.00 0.04 28 11501 0.03 0.24 8 3067.3 0.10 0.80 GO_REGULATION_OF_CATABOLIC_PROCESS 54 20833 0.01 0.10 33 13205 0.07 0.31 21 7628.7 0.08 0.74 GO_RESPONSE_TO_KETONE 21 8843 0.00 0.04 18 7837.3 0.01 0.20 3 1005.7 0.48 1.00 GO_POSITIVE_REGULATION_OF_CELL_ADHESION 21 8588.5 0.01 0.09 19 7667.5 0.12 0.39 2 921.03 0.14 0.88 GO_RESPONSE_TO_HORMONE 79 29962 0.01 0.09 55 22279 0.01 0.21 24 7683.7 0.53 1.00 GO_BLOOD_VESSEL_MORPHOGENESIS 30 12059 0.01 0.08 25 10245 0.05 0.28 5 1813.7 0.26 1.00 GO_RESPONSE_TO_ESTROGEN 20 8429.9 0.00 0.04 14 5989.2 0.03 0.23 6 2440.7 0.06 0.68 GO_RESPONSE_TO_RADIATION 21 9009 0.00 0.03 19 8327.5 0.00 0.15 2 681.51 0.40 1.00 GO_RESPONSE_TO_EXTRACELLULAR_STIMULUS 58 22855 0.00 0.03 38 15652 0.01 0.21 20 7204 0.10 0.80 GO_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND 28 11402 0.01 0.05 22 9147.5 0.03 0.24 6 2254.5 0.16 0.92 GO_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY 61 23692 0.01 0.05 39 15895 0.02 0.21 22 7797.4 0.12 0.85 GO_VASCULATURE_DEVELOPMENT 32 12980 0.00 0.04 27 11166 0.02 0.22 5 1813.7 0.26 1.00 GO_RESPONSE_TO_ABIOTIC_STIMULUS 63 25227 0.00 0.02 48 19967 0.00 0.14 15 5260.1 0.20 0.98 GO_RESPONSE_TO_DRUG 47 18305 0.01 0.09 29 12241 0.00 0.19 18 6064 0.31 1.00 GO_RESPONSE_TO_GROWTH_FACTOR 23 9758.3 0.00 0.03 18 8031.8 0.00 0.14 5 1726.5 0.36 1.00 GO_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS 73 28292 0.00 0.04 52 21388 0.01 0.19 21 6904.6 0.41 1.00 GO_TRANSMEMBRANE_RECEPTOR_PROTEIN_TYROSINE_KINASE_(—) 23 9498.8 0.01 0.05 19 7969.4 0.03 0.24 4 1529.4 0.19 0.98 SIGNALING_PATHWAY GO_CELLULAR_RESPONSE_TO_PEPTIDE 21 8753.6 0.01 0.05 18 7556.8 0.03 0.24 3 1196.7 0.17 0.95 GO_HEXOSE_METABOLIC_PROCESS 21 8616.8 0.01 0.08 13 5865.8 0.00 0.14 8 2751 0.33 1.00 GO_CELLULAR_RESPONSE_TO_STRESS 87 33202 0.01 0.05 63 25236 0.02 0.21 24 7965.7 0.36 1.00 GO_ENDOCYTOSIS 44 17555 0.00 0.04 39 15854 0.02 0.23 5 1701.1 0.39 1.00 GO_CIRCULATORY_SYSTEM_DEVELOPMENT 41 16113 0.01 0.08 34 13665 0.06 0.28 7 2448.2 0.31 1.00 GO_RESPONSE_TO_STARVATION 26 10695 0.00 0.05 22 9438.5 0.01 0.21 4 1256.2 0.54 1.00 GO_HEMOSTASIS 27 11311 0.00 0.03 24 10276 0.00 0.19 3 1035.4 0.43 1.00 GO_RESPONSE_TO_MOLECULE_OF_BACTERIAL_ORIGIN 28 11380 0.01 0.06 22 9029.7 0.06 0.28 6 2349.8 0.10 0.80 NA 20 8636.2 0.00 0.03 19 8175.6 0.01 0.21 1 460.52 0.38 1.00 GO_CELL_SURFACE 42 16481 0.01 0.08 37 14367 0.20 0.49 5 2114.3 0.04 0.60 GO_PEPTIDASE_REGULATOR_ACTIVITY 26 10611 0.01 0.06 20 8341.2 0.04 0.25 6 2269.3 0.15 0.91 NA.1 20 8196.3 0.01 0.09 14 5686.3 0.14 0.43 6 2509.9 0.03 0.48 GO_MOLECULAR_FUNCTION_REGULATOR 77 30265 0.00 0.02 57 22685 0.04 0.25 20 7579.9 0.03 0.48 GO_PEPTIDASE_INHIBITOR_ACTIVITY 22 9121.8 0.01 0.05 19 7880.7 0.05 0.28 3 1241.1 0.14 0.88 GO_PHOSPHOLIPID_BINDING 21 8989.6 0.00 0.03 12 4844.9 0.19 0.47 9 4144.7 0.00 0.05 HALLMARK_TNFA_SIGNALING_VIA_NFKB 37 14438 0.02 0.10 33 13859 0.00 0.08 4 579.08 1.00 1.00

TABLE 11 Pathway enrichments shared between APAP and PH. Genes. Stat.non. p.non. padj.non. Genes. Stat.mix. p.mix. padj.mix. Genes. Stat.mix. p.mix. padj.mix. tot._(—) dir.._(—) dir.._(—) dir.._(—) up._(—) dir.up._(—) dir.up._(—) dir.up._(—) down._(—) dir.dn._(—) dir.dn._(—) dir.dn._(—) APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP APAP GO_NEGATIVE_REGULATION_OF_PROTEOLYSIS 4.3 12343 0.00 0.03 34 10537 0.00 0.01 9 1806.5 0.56 1.00 GO_CHEMICAL_HOMEOSTASIS 112 30618 0.00 0.01 77 22096 0.00 0.01 35 8522.2 0.10 0.63 GO_SECRETION_BY_CELL 46 13917 0.00 0.01 41 12965 0.00 0.00 5 952.32 0.59 1.00 GO_REGULATION_OF_HYDROLASE_ACTIVITY 118 30643 0.00 0.03 92 24535 0.01 0.05 26 6108.3 0.20 0.75 GO_REGULATION_OF_BODY_FLUID_LEVELS 49 14206 0.00 0.01 41 12431 0.00 0.01 8 1775 0.41 0.94 GO_HOMEOSTATIC_PROCESS 150 40881 0.00 0.00 105 29582 0.00 0.00 45 11298 0.04 0.53 GO_WOUND_HEALING 58 16314 0.00 0.02 51 14915 0.00 0.02 7 1398.7 0.56 1.00 GO_GLYCEROLIPID_METABOLIC_PROCESS 59 17149 0.00 0.01 40 11310 0.02 0.09 19 5839.1 0.00 0.26 GO_RESPONSE_TO_EXTERNAL_STIMULUS 166 41066 0.01 0.08 113 28480 0.05 0.19 53 12586 0.10 0.63 GO_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND 186 45695 0.01 0.09 124 32182 0.01 0.05 62 13512 0.34 0.90 GO_RESPONSE_TO_LIPID 120 30247 0.01 0.09 82 22400 0.00 0.03 38 7846.9 0.56 1.00 GO_NEUTRAL_LIPID_METABOLIC_PROCESS 34 10847 0.00 0.01 20 6084.9 0.02 0.09 14 4762.1 0.00 0.26 GO_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY 57 16248 0.00 0.01 43 12401 0.00 0.04 14 3847.1 0.07 0.56 GO_ION_HOMEOSTASIS 65 17747 0.00 0.04 47 13484 0.01 0.04 18 4262.7 0.23 0.80 GO_RESPONSE_TO_BIOTIC_STIMULUS 83 21979 0.01 0.05 60 15941 0.03 0.13 23 6037.9 0.05 0.56 GO_EXOCYTOSIS 36 10787 0.00 0.02 32 10043 0.00 0.01 4 743.54 0.59 1.00 GO_PLATELET_DEGRANULATION 31 10055 0.00 0.01 28 9340.2 0.00 0.01 3 714.91 0.36 0.91 GO_RESPONSE_TO_ALCOHOL 65 17315 0.01 0.07 48 13614 0.01 0.04 17 3701.2 0.42 0.94 GO_REGULATED_EXOCYTOSIS 33 10189 0.00 0.01 30 9473.9 0.00 0.02 3 714.91 0.36 0.91 GO_NEGATIVE_REGULATION_OF_PEPTIDASE_ACTIVITY 37 10915 0.00 0.03 28 9108.3 0.00 0.01 9 1806.5 0.56 1.00 GO_EXTRACELLULAR_MATRIX 29 8933.1 0.00 0.02 24 7347.9 0.01 0.05 5 1585.2 0.07 0.56 GO_SECRETORY_GRANULE 38 11617 0.00 0.01 33 10766 0.00 0.01 5 851.27 0.70 1.00 GO_PLATELET_ALPHA_GRANULE 20 6903.9 0.00 0.01 20 6903.9 0.00 0.01 0 NA NA NA GO_SECRETORY_GRANULE_LUMEN 25 8665.9 0.00 0.01 23 8340.8 0.00 0.00 2 325.07 0.62 1.00 GO_SECRETORY_VESICLE 46 12933 0.00 0.04 39 11952 0.00 0.01 7 980.73 0.88 1.00 GO_VESICLE_LUMEN 34 12292 0.00 0.00 29 10917 0.00 0.00 5 1375.6 0.18 0.74 GO_BLOOD_MICROPARTICLE 45 15877 0.00 0.00 37 13416 0.00 0.00 8 2460.8 0.05 0.55 GO_INTRACELLULAR_VESICLE 134 33750 0.01 0.07 109 27946 0.03 0.12 25 5804.5 0.24 0.81 GO_EXTRACELLULAR_SPACE 158 47392 0.00 0.00 111 35581 0.00 0.00 47 11811 0.03 0.52 GO_CYTOPLASMIC_VESICLE_PART 70 19517 0.00 0.01 60 16840 0.00 0.04 10 2676.2 0.12 0.66 GO_PROTEIN_LIPID_COMPLEX 22 7615.8 0.00 0.01 11 4064.5 0.00 0.01 11 3551.4 0.01 0.38 GO_ENZYME_INHIBITOR_ACTIVITY 46 13024 0.00 0.03 36 10396 0.01 0.06 10 2628.1 0.14 0.68 GO_ENZYME_REGULATOR_ACTIVIIY 92 24477 0.00 0.03 70 18618 0.02 0.11 22 5858.4 0.05 0.55 HALLMARK_HYPOχIA 31 8762.2 0.02 0.06 25 7882 0.00 0.01 6 880.21 0.83 0.99 HALLMARK_APOPTOSIS 33 9090.3 0.02 0.07 25 6879.2 0.07 0.15 8 2211.1 0.12 0.80 HALLMARK_COMPLEMENT 44 12175 0.01 0.04 36 10358 0.01 0.03 8 1816.6 0.37 0.84 Genes. Stat.non. p.non. padj.non. Genes. Stat.mix. p.mix. padj.mix. Genes. Stat.mix. p.mix. padj.mix. tot._(—) dir.._(—) dir.._(—) dir.._(—) up._(—) dir.up._(—) dir.up._(—) dir.up._(—) down._(—) dir.dn._(—) dir.dn._(—) dir.dn._(—) PH PH PH PH PH PH PH PH PH PH PH PH GO_NEGATIVE_REGULATION_OF_PROTEOLYSIS 32 13244 0.00 0.03 26 10935 0.01 0.21 6 2308.3 0.13 0.85 GO_CHEMICAL_HOMEOSTASIS 70 26876 0.01 0.06 48 18932 0.09 0.34 22 7944.6 0.08 0.75 GO_SECRETION_BY_CELL 35 14350 0.00 0.03 28 11419 0.05 0.27 7 2930.8 0.03 0.48 GO_REGULATION_OF_HYDROLASE_ACTIVITY 79 31167 0.00 0.02 58 23315 0.02 0.21 21 7852 0.03 0.48 GO_REGULATION_OF_BODY_FLUID_LEVELS 38 15254 0.00 0.04 32 13261 0.01 0.21 6 1993.5 0.43 1.00 GO_HOMEOSTATIC_PROCESS 87 33210 0.01 0.05 55 21855 0.05 0.27 32 11356 0.08 0.74 GO_WOUND_HEALING 39 15745 0.00 0.03 33 13681 0.01 0.21 6 2063.7 0.35 1.00 GO_GLYCEROLIPID_METABOLIC_PROCESS 38 15218 0.00 0.04 22 8957.4 0.08 0.31 16 6260.9 0.01 0.38 GO_RESPONSE_TO_EXTERNAL_STIMULUS 117 44970 0.00 0.03 87 34412 0.02 0.21 30 10558 0.11 0.81 GO_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND 117 44639 0.00 0.03 80 31974 0.01 0.21 37 12664 0.16 0.92 GO_RESPONSE_TO_LIPID 74 28488 0.01 0.05 51 20165 0.07 0.31 23 8323.5 0.07 0.71 GO_NEUTRAL_LIPID_METABOLIC_PROCESS 26 10471 0.01 0.09 11 4670.9 0.06 0.30 15 5800.4 0.03 0.48 GO_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY 39 15809 0.00 0.03 29 11659 0.07 0.31 10 4150.4 0.01 0.38 GO_ION_HOMEOSTASIS 36 14581 0.00 0.03 28 11124 0.12 0.39 8 3456.5 0.01 0.34 GO_RESPONSE_TO_BIOTIC_STIMULUS 53 21055 0.00 0.03 42 17231 0.01 0.21 11 3824.1 0.26 1.00 GO_EXOCYTOSIS 29 12266 0.00 0.02 24 9996.6 0.02 0.21 5 2269.4 0.01 0.38 GO_PLATELET_DEGRANULATION 28 11805 0.00 0.02 23 9536.1 0.03 0.24 5 2269.4 0.01 0.38 GO_RESPONSE_TO_ALCOHOL 42 16602 0.01 0.06 30 12215 0.04 0.26 12 4387.7 0.13 0.85 GO_REGULATED_EXOCYTOSIS 29 12266 0.00 0.02 24 9996.6 0.02 0.21 5 2269.4 0.01 0.38 GO_NEGATIVE_REGULATION_OF_PEPTIDASE_ACTIVITY 30 12322 0.00 0.03 24 10014 0.02 0.21 6 2308.3 0.13 0.85 GO_EXTRACELLULAR_MATRIX 23 9693.5 0.00 0.03 15 6421.9 0.03 0.23 8 3271.7 0.03 0.48 GO_SECRETORY_GRANULE 31 12775 0.00 0.03 26 10505 0.07 0.31 5 2269.4 0.01 0.38 GO_PLATELET_ALPHA_GRANULE 21 8854.2 0.00 0.04 20 8393.7 0.03 0.23 1 460.52 0.38 1.00 GO_SECRETORY_GRANULE_LUMEN 25 10906 0.00 0.02 21 9096.7 0.00 0.18 4 1808.8 0.03 0.48 GO_SECRETORY_VESICLE 33 13409 0.00 0.04 27 10966 0.06 0.28 6 2443.2 0.06 0.68 GO_VESICLE_LUMEN 34 14920 0.00 0.02 29 12650 0.00 0.10 5 2269.4 0.01 0.38 GO_BLOOD_MICROPARTICLE 44 19027 0.00 0.02 36 15505 0.00 0.14 8 3521.8 0.00 0.24 GO_INTRACELLULAR_VESICLE 75 29546 0.00 0.03 57 22628 0.04 0.27 18 6917.8 0.02 0.44 GO_EXTRACELLULAR_SPACE 126 49402 0.00 0.02 90 36270 0.00 0.14 36 13132 0.02 0.48 GO_CYTOPLASMIC_VESICLE_PART 49 19540 0.00 0.03 38 15441 0.03 0.23 11 4098.9 0.11 0.80 GO_PROTEIN_LIPID_COMPLEX 20 8548.6 0.00 0.03 11 4585.6 0.10 0.37 9 3963 0.00 0.23 GO_ENZYME_INHIBITOR_ACTIVITY 35 14558 0.00 0.02 27 11014 0.05 0.27 8 3543.7 0.00 0.23 GO_ENZYME_REGULATOR_ACTIVITY 68 26821 0.00 0.03 49 19383 0.07 0.31 19 7437.9 0.01 0.38 HALLMARK_HYPOXIA 32 12844 0.01 0.10 29 12176 0.01 0.09 3 668.01 0.90 1.00 HALLMARK_APOPTOSIS 21 8486.6 0.02 0.10 14 5742.2 0.11 0.32 7 2744.4 0.08 0.53 HALLMARK_COMPLEMENT 22 8854.8 0.02 0.10 19 7868.5 0.05 0.30 3 986.27 0.50 0.99

scRNA-seq is a powerful tool for the assessment of transcriptional changes following a perturbation, such as acute injury; however, the spatial location of each cell is lost following dissociation of the liver. Therefore, Applicants next wanted to validate, quantify, and spatially resolve genes of interest identified in the scRNA-Seq data set by performing smFISH analysis for select genes that span essential hepatic functions including: anti-oxidant response (Mt1, Txnrd1, Srxn1, Gclc), serum protein synthesis (Alb), glucose homeostasis (Pck1, Slc2a2), glutamate metabolism (Glut), and clotting factor synthesis (F2). Genes known to have either pericentral (Cyp2e1, Glu1, Sox9) or periportal (Lgr5, Tbx3, Axing, Arg1, Cdh1, Gls2, Ppargc1a) localization, as well as genes thought to be markers for hepatic stem cells (Sox9, Tbx3, Lgr5, Axing) are also targets. Applicants conducted a combinatorial analysis of smFISH by using an algorithm to define cellular outlines (CellProfiler) and counting transcripts (FISH-quant) to allow for a high-throughput method for analyzing the large number of genes that span many liver functions. FISH-quant was used to convert spot counts from every cell outline defined by CellProfiler into a representative heat map of the liver lobule for a given gene (e.g. Cyp2e1 and Glu1, FIG. 3C). smFISH analysis confirms the loss of the Cyp2e1-positive cell population directly surrounding the central vein in the APAP model at 6 and 24 hrs following exposure. Interestingly, the Cyp2e1-positive area spans an increased number of cells at 24 and 48 hrs post-APAP. This can be further confirmed by comparing the number of transcripts/area from a defined reference point (central vein) (FIG. 3C). Expression of Cyp2e1 reaches further into the midzone of the liver lobule following injury of the area directly surrounding the central vein in the APAP model. This phenomenon is further evident in the PH model in which the number of Cyp2e1-positive cells span further into the midzone of the liver lobule along with a dramatic increase in the number of Cyp2e1 transcripts/area. This suggests that midzonal and periportal hepatocytes have the ability to adapt to a loss of hepatocytes by upregulating genes that may not be normally expressed in that particular cell population (or zone) of the liver lobule.

Another example of functional plasticity is the expression of glutamate synthetase (Glut). As mentioned previously, Glu1 is normally expressed in a one cell thick layer of cells directly surrounding the central vein. As expected, this population of cells is eliminated following APAP exposure (6 and 24 hr post-APAP) (FIG. 3A). However, a small, but significant, amount of up-regulation of Glu1 can be observed in hepatocytes that span the entire liver lobule at both of these time points. This is further confirmed by the number of transcripts/area measured (FIG. 3C). The Glut-positive area returns to be primarily localized around the central vein by 48 hrs post-APAP. Interestingly, the PH model confirms the plasticity of hepatocytes in regard to Glu1 expression by revealing a marked up-regulation of the gene in pericentral hepatocytes, but also in midzonal hepatocytes, in which it is not normally expressed.

The status of functional hepatic marker genes was assessed in order to define the kinetics of transcriptional changes in an injury-dependent manner (FIG. 4 ). It is not surprising that select functions appear to be driven by injury mechanisms. For example, the anti-oxidant response appears to be strongest in the zone-dependent (APAP) model. This can be explained by the generation of ROS in this model, which drives the injury mechanism. Genes such as thioredoxin (Txnrd1) and sulfiredoxin (Srxn1) are classic anti-oxidant response genes that are most extremely up-regulated in the zone-dependent (APAP) model. However, there are an increased number of cells expressing these genes in the zone-independent (PH) model suggesting that there is still a compensatory expansion of expression due to the loss of functional tissue. It is also interesting to note that smFISH data reveals an up-regulation of these genes across the liver lobule reaching into the periportal region in the APAP model. This suggests that the compensatory up-regulation is not exclusive to the area surrounding injury, but that all hepatocytes can respond in a similar fashion.

A similar functional compensatory response can be seen for other classic hepatic marker genes (FIG. 4 ). Albumin, the most abundant serum protein, is produced by hepatocytes across the liver lobule with the highest expression in the periportal region. Acute injury results in a marked up-regulation of albumin across the entire liver lobule for both models. However, this up-regulation is most extreme in the PH model. Without being bound by theory, it is believed that this is due to differences in the amount of functional tissue loss between the two models. The PH model results in a much larger loss of functional tissue resulting in a higher demand for compensation. Similar observations can be made for genes such as the gluconeogenesis gene Pck1 and the coagulation factor F2.

One of the most dramatically changed genes following acute injury in both the zone-dependent (APAP) and -independent (PH) models is metallothionein (Mt1). Metallothionein has a high affinity for bivalent cations in the liver. It is thought to play an important role in the anti-oxidant response by providing a reservoir for bivalent cations in order to activate metalloenzymes, such as superoxide dismutase. Also, Mt1 has been shown to be induced following cellular damage and during the regenerative response where it is thought to provide cations for transcription factor and growth factor function. Applicants observe a massive increase in the expression of Mt1 in both zone-dependent (APAP) and -independent (PH) injury models within the earliest time points examined. The up-regulation of Mt1 happens in all hepatocytes highlighting not only the rapidity of hepatic functional adaptation, but also, the plasticity of the majority of hepatocytes across the liver lobule. MU expression returns to normal at 24 hrs post-APAP exposure, but can then be found in an increased number of hepatocytes at both 48 and 96 hrs post-APAP. This suggests that a second wave of Mt1 expression is important during the cell proliferation response. This is corroborated by the observation that Mt1 expression remains elevated throughout the PH time course, where an increased demand is present due to the increased loss of cell mass in this model.

Hepatic Functional Compensation and Hepatocyte Proliferation

Liver function is known to be maintained with only slight alterations following acute liver injury. Here, Applicants describe a functional adaptive response throughout a time course of recovery. An important hallmark of liver regeneration is the ability for hepatocytes to proliferate following acute injury. This has been the most well-studied characteristic of liver regeneration to date. However, little is known about the maintenance of function within hepatocytes that are actively dividing. To investigate this, Applicants have performed a combinatorial analysis of gene expression (smFISH) and proliferation (PCNA immunofluorescence) in order to assess whether hepatocytes have the ability to both functionally adapt to a loss of tissue while maintaining the ability to proliferate or if these are mutually exclusive events. (See, e.g. FIGS. 6D, 6E, 16 )

Mechanisms Surrounding the Maintenance of Liver Function: A Novel Dual Role for Wnt Signaling

The next aim was to identify potential signaling cascades that respond to acute liver injury to promote both functional adaptation through transcriptional changes and promotion of cell proliferation to replenish lost cell mass. The Wnt signaling pathway fits both categories as it is known to play an important role in both the establishment of hepatic zonation as well as being necessary for the cell proliferation response during hepatic regeneration. This suggests that Wnt signaling may play a dual role in the liver following acute injury by which it not only promotes cell proliferation and a return to pre-injury cell number and mass but that the pathway also activates reprogramming of already present hepatocytes to maintain essential hepatic function. (FIG. 8A-8C)

The study in this example provides a novel view of liver regeneration revealing a functional compensatory response to lost functional mass during acute liver injury.

Methods

Liver dissociation: At time period for evaluation post-injury, liver was dissociated by the following steps: Anesthetize mouse, Open abdomen, Clamp the thoracic inferior vena cava, Insert catheter into abdominal inferior vena cava, Perfuse liver with perfusion medium and cut portal vein for drainage, Perfuse liver with digestion medium, Remove liver.

Study of gene expression patterns across liver lobule followed the general approach of K B Halpern et al. Nature 1-5 (2017) doi:10.1038/nature21065, defining a spatial barcode of zonated landmark genes in untreated mice. This approach was utilized as a starting point for the study of gene expression patterns in the PH and APAP injured livers.

Example 2—High Fat Diet as Model for Chronic Injury

As provided in FIG. 17A, future studies will be used to extend the investigation described in Example 1 to biologically expand analysis to other organs and from acute injury to chronic injury. High fat diets can lead to liver and intestinal inflammation and cancer. Use of High Fat Diet mouse models will extend the approach from profiling alone to multiple GI and immune issues in a chronic injury model, allowing identification and characterization of potential cancer progenitors in the gut and liver. Utilization of this model will allow exploration of cross-talk between GI organs through immune cells, hormones, or other molecules (e.g. bile acids. A schematic of a protocol that can be used in biological expansion studies utilizing high fat diet will include study of multiple organs including liver and intestines with subsequent sorting of cells, peripheral blood, and spleen and bone marrow (pilot only) (FIG. 17C). Distinct cell types and shift in expression between control diet and high fat diet subjects can be identified, including clustering of intestinal, liver and immune cell types and shifts by diets in particular cell types using approaches disclosed herein.

Further studies can identify reproducible shifts in cell types or expression patterns between diet conditions. Hepatic organoid assays will be performed to assess organoid forming efficiency and effect of lipids on organoid growth. Use of smFISH or IHC imaging to further characterize genes/proteins and pathways of interest in space would be a further goal of the extended biological studies.

Example 3—Acute Injury

Applicants investigated compensatory responses in the liver during key phases of liver regeneration in both a toxic (APAP) model and following surgical resection (partial hepatectomy, PH) (FIG. 18A). Utilizing the powerful combinatorial approach of Seq-Well, a massively-parallel single-cell RNA-seq (scRNA-Seq) platform ideally suited for fragile cells like hepatocytes, and single-molecule fluorescent in situ hybridization (smFISH), Applicants define transcriptional changes after injury⁹. Disclosed herein is the discovery that remaining hepatocytes functionally compensate for lost liver mass by increased transcriptional output of key hepatocyte genes. Importantly, hepatocytes also alter their zone-dictated functional identities within the liver lobule to help maintain global expression of select transcripts. These studies find that hepatocyte functional compensation precedes the peak phase of cell proliferation and that cycling cells do not participate to the same degree as non-cycling hepatocytes during the regeneration phase. Both cycling and non-cycling cells show upregulation of targets of Wnt signaling—known to play a central role in normal hepatocyte development, maintenance and liver regeneration. Applicants demonstrate that compensation depends on intact β-catenin activation through macrophage-secreted Wnts. Overall, our results identify previously unappreciated plasticity among hepatocytes during a newly discovered compensatory phase after liver injury, as well as Wnt/β-catenin signaling as a therapeutically relevant pathway for maintaining and re-establishing homeostatic liver function.

Transcriptional Adaption after Liver Injury

To assess global transcriptional shifts in hepatocytes at single-cell resolution following acute liver injury, Applicants employed scRNA-Seq to characterize response dynamics in both PH and APAP models, capturing the injury, regeneration, and termination phases of liver regeneration⁴ (FIG. 18B, 18C). Applicants profiled a total of 16,019 cells across 19 different experiments to an average sequencing depth of >48,000 reads/cell (FIG. 24A-24C, Methods). Immune and endothelial cell types as well as low quality cells were filtered out from the dataset, retaining 10,762 high-quality hepatocyte transcriptomes for subsequent analyses (FIG. 24D, 24E, Table 12, Methods). Shared nearest neighbour clustering (SNN) visualized on a t-Stochastic Neighbor Embedding (t-SNE) plot revealed hepatocyte populations that cluster by injury model and post-injury time point (FIG. 18D, Methods).

TABLE 12 Sequencing metrics table containing Average reads, Average genes, Average UMIs, and total number of cells passing quality and hepatocyte identitiy filtering for each sample in the dataset. Ave Ave Ave Sample ReadsAll GenesAll UMIsAll nCellsFil UTM1 29350 2345 11709 1188 UTM5 31794 1705 8312 1435 UTM6 79301 892 4003 778 A6M1 34132 1298 6010 291 A6M2 27584 1315 5696 128 A24M1 34357 1948 9366 852 A24M2 18777 828 3997 191 A48M1 28188 2490 14543 790 A48M2 54952 1536 14358 120 A96M1 35995 2165 11572 757 A96M2 441 126 441 52 PHX3M1 99976 3320 35423 249 PHX3M2 20333 2149 10102 1330 PHX3M3 92468 3222 32670 266 PHX48M1 11125 1139 5850 165 PHX48M2 54248 1976 12051 440 PHX48M3 92468 1324 6648 352 PHX120M1 93284 3216 26576 287 PHX120M2 22696 1826 8031 1091

TABLE 13 Differentially expressed genes (DEG) between the three untreated (UT) samples. Calculated using the FindAllMarkers function in the R package Seurat using the Wilcox test. p_val avg_logFC pct.1 pct.2 p_val_adj cluster gene Thrsp 0 1.21818366 0.977 0.439 0 UTM1 Thrsp Nudt7 0 1.11928024 0.998 0.74 0 UTM1 Nudt7 Scd1 0 0.99322463 1 0.848 0 UTM1 Scd1 Hsd3b5 0 0.97409205 0.944 0.396 0 UTM1 Hsd3b5 Cfhr2 0 0.81994799 0.998 0.798 0 UTM1 Cfhr2 Uox 0 0.71024072 0.999 0.947 0 UTM1 Uox Trf 0 0.52918211 1 1 0 UTM1 Trf Aadac  7.97E−305 0.81646299 0.999 0.786  1.98E−300 UTM1 Aadac Gnmt  4.34E−304 0.52785298 1 0.982  1.08E−299 UTM1 Gnmt Inmt  1.17E−288 0.82783916 0.998 0.822  2.90E−284 UTM1 Inmt Alb  3.66E−274 0.48743601 1 1  9.08E−270 UTM1 Alb Car3  1.52E−269 0.59669431 1 0.96  3.78E−265 UTM1 Car3 Keg1  6.58E−250 0.78906431 0.896 0.357  1.63E−245 UTM1 Keg1 Acly  4.57E−246 0.76348807 0.815 0.246  1.14E−241 UTM1 Acly Sc5d  3.32E−228 0.7161617 0.984 0.665  8.24E−224 UTM1 Sc5d Cyp7a1  2.92E−219 0.61454812 0.59 0.081  7.25E−215 UTM1 Cyp7a1 Otc  1.35E−217 0.55985355 0.998 0.869  3.34E−213 UTM1 Otc Akr1c6  5.76E−213 0.53304224 1 0.955  1.43E−208 UTM1 Akr1c6 G6pc  3.04E−212 0.68559678 0.976 0.631  7.55E−208 UTM1 G6pc Cyp2c70  4.92E−202 0.63146884 0.988 0.751  1.22E−197 UTM1 Cyp2c70 Atp5f1  2.34E−201 0.57886961 0.995 0.801  5.80E−197 UTM1 Atp5f1 Fbp1  6.59E−199 0.51619137 0.998 0.906  1.64E−194 UTM1 Fbp1 Fabp1  5.43E−197 0.309557 1 1  1.35E−192 UTM1 Fabp1 Hsd11b1  2.73E−196 0.56232512 0.994 0.811  6.77E−192 UTM1 Hsd11b1 Adipor2  7.77E−196 0.63114559 0.98 0.714  1.93E−191 UTM1 Adipor2 Serpina3c  1.06E−195 0.50459729 0.755 0.186  2.64E−191 UTM1 Serpina3c Sepp1  2.79E−195 0.28399703 1 1  6.92E−191 UTM1 Sepp1 Aacs  5.61E−195 0.40975071 0.441 0.032  1.39E−190 UTM1 Aacs Mgst1  1.31E−193 0.47663366 1 0.996  3.24E−189 UTM1 Mgst1 Fasn  2.04E−186 0.55115081 0.675 0.168  5.06E−182 UTM1 Fasn Egfr  1.52E−185 0.64603405 0.981 0.716  3.79E−181 UTM1 Egfr Hhex  1.16E−184 0.49641357 0.63 0.134  2.87E−180 UTM1 Hhex Fh1  1.19E−179 0.62319183 0.929 0.498  2.96E−175 UTM1 Fh1 Cat  7.06E−179 0.43531632 0.999 0.955  1.75E−174 UTM1 Cat Errfi1  2.37E−173 0.51395691 0.997 0.864  5.88E−169 UTM1 Errfi1 Ddc  1.65E−172 0.56196541 0.791 0.282  4.10E−168 UTM1 Ddc Elovl2  1.71E−170 0.58928921 0.947 0.566  4.24E−166 UTM1 Elovl2 Prdx4  9.64E−163 0.6055411 0.884 0.458  2.39E−158 UTM1 Prdx4 Cth  6.01E−162 0.54591986 0.991 0.756  1.49E−157 UTM1 Cth Cps1  8.04E−162 0.43042778 1 0.956  2.00E−157 UTM1 Cps1 Igf1  3.51E−161 0.47768807 0.994 0.855  8.71E−157 UTM1 Igf1 Bhmt  6.12E−161 0.43322273 0.999 0.934  1.52E−156 UTM1 Bhmt Mup3  1.14E−159 0.34482089 1 1  2.84E−155 UTM1 Mup3 Elovl5  8.41E−159 0.61224151 0.868 0.425  2.09E−154 UTM1 Elovl5 Cyp2f2  1.40E−158 0.60967373 0.982 0.799  3.48E−154 UTM1 Cyp2f2 Fgb  2.78E−158 0.28109091 1 1  6.90E−154 UTM1 Fgb Serpind1  2.39E−156 0.53913725 0.974 0.676  5.94E−152 UTM1 Serpind1 Echdc2  8.02E−154 0.52918421 0.796 0.315  1.99E−149 UTM1 Echdc2 Hspa5  2.56E−153 0.43540717 0.999 0.914  6.36E−149 UTM1 Hspa5 Slc10a1  1.72E−152 0.51702656 0.987 0.765  4.27E−148 UTM1 Slc10a1 Serp1  1.63E−151 0.55530728 0.944 0.601  4.05E−147 UTM1 Serp1 Aqp8  2.56E−150 0.5507968 0.817 0.338  6.36E−146 UTM1 Aqp8 Slco1a1  4.64E−150 0.52689959 0.97 0.674  1.15E−145 UTM1 Slco1a1 C9  8.51E−150 0.43561512 0.995 0.908  2.11E−145 UTM1 C9 Cstf3  1.59E−143 0.3219351 0.423 0.058  3.95E−139 UTM1 Cstf3 Mdh1  6.57E−143 0.46155291 0.988 0.832  1.63E−138 UTM1 Mdh1 Hmgcr  1.22E−142 0.42082632 0.545 0.126  3.04E−138 UTM1 Hmgcr Hsd17b6  1.38E−142 0.52097308 0.769 0.284  3.42E−138 UTM1 Hsd17b6 Qdpr  2.12E−141 0.50438731 0.982 0.723  5.28E−137 UTM1 Qdpr Hrsp12  1.29E−140 0.44167003 0.995 0.908  3.20E−136 UTM1 Hrsp12 Serpinc1  1.43E−140 0.32566392 1 0.974  3.54E−136 UTM1 Serpinc1 Hes6  7.04E−140 0.46539249 0.722 0.258  1.75E−135 UTM1 Hes6 1500017E21Rik  4.96E−139 0.54206772 0.774 0.317  1.23E−134 UTM1 1500017E21Rik Gm4788  8.33E−139 0.49918037 0.965 0.659  2.07E−134 UTM1 Gm4788 Tubb2a  1.08E−138 0.473813 0.735 0.268  2.68E−134 UTM1 Tubb2a Deb1  3.87E−135 0.49455146 0.737 0.285  9.61E−131 UTM1 Deb1 Ttc39c  8.05E−135 0.5016707 0.907 0.501  2.00E−130 UTM1 Ttc39c Ndufv2  1.68E−134 0.5030504 0.905 0.51  4.18E−130 UTM1 Ndufv2 Ndufc2  1.17E−133 0.54556827 0.86 0.428  2.90E−129 UTM1 Ndufc2 Aldob  2.10E−133 0.27645126 1 0.995  5.22E−129 UTM1 Aldob Gls2  1.90E−130 0.54901012 0.91 0.522  4.71E−126 UTM1 Gls2 Arg1  1.92E−129 0.33011144 1 0.972  4.76E−125 UTM1 Arg1 Ass1  2.99E−127 0.37456042 0.998 0.942  7.42E−123 UTM1 Ass1 Hmgcs1  5.26E−125 0.52691875 0.932 0.581  1.31E−120 UTM1 Hmgcs1 B2m  5.63E−124 0.35038582 0.999 0.944  1.40E−119 UTM1 B2m Selk  5.20E−122 0.4300711 0.773 0.332  1.29E−117 UTM1 Selk Cfhr1  3.40E−121 0.48091782 0.838 0.43  8.44E−117 UTM1 Cfhr1 Insig1  3.75E−121 0.42772787 0.713 0.272  9.31E−117 UTM1 Insig1 Ndufs4  9.96E−120 0.4886043 0.831 0.418  2.47E−115 UTM1 Ndufs4 Sqle  1.16E−119 0.40342481 0.623 0.202  2.88E−115 UTM1 Sqle Tat  7.79E−119 0.41673949 0.994 0.854  1.93E−114 UTM1 Tat Vmp1  1.20E−118 0.44115404 0.765 0.329  2.99E−114 UTM1 Vmp1 Aox3  1.82E−117 0.43544215 0.99 0.843  4.52E−113 UTM1 Aox3 Adh6-ps1  5.83E−117 0.37703004 0.577 0.172  1.45E−112 UTM1 Adh6-ps1 C1d  9.18E−117 0.38281513 0.626 0.208  2.28E−112 UTM1 C1d Slc22a30  1.04E−116 0.40119661 0.779 0.338  2.58E−112 UTM1 Slc22a30 Tmem30a  8.89E−116 0.46673515 0.899 0.538  2.21E−111 UTM1 Tmem30a D4Wsu53e  2.39E−115 0.38697768 0.671 0.232  5.93E−111 UTM1 D4Wsu53e Hacl1  1.19E−113 0.43962629 0.971 0.703  2.95E−109 UTM1 Hacl1 Cml1  1.24E−113 0.46331845 0.949 0.654  3.08E−109 UTM1 Cml1 Cmtm6  1.39E−113 0.36019667 0.614 0.204  3.45E−109 UTM1 Cmtm6 H2-K1  1.60E−112 0.36327199 1 0.902  3.97E−108 UTM1 H2-K1 2810007J24Rik  5.68E−112 0.36295773 0.997 0.913  1.41E−107 UTM1 2810007J24Rik Cxadr  1.23E−111 0.38792689 0.607 0.204  3.05E−107 UTM1 Cxadr Stard4  2.16E−111 0.3943334 0.67 0.253  5.35E−107 UTM1 Stard4 Slc26a1  1.22E−108 0.42555394 0.776 0.343  3.02E−104 UTM1 Slc26a1 Ppib  1.80E−106 0.42232707 0.955 0.666  4.47E−102 UTM1 Ppib Hao1  4.36E−105 0.41128035 0.944 0.658  1.08E−100 UTM1 Hao1 Nit2  5.05E−105 0.41499963 0.836 0.437  1.25E−100 UTM1 Nit2 Gas2  9.53E−105 0.40152064 0.614 0.221  2.37E−100 UTM1 Gas2 Eny2  3.13E−104 0.3871366 0.706 0.292  7.77E−100 UTM1 Eny2 Lifr  1.83E−103 0.4005345 0.91 0.578 4.54E−99 UTM1 Lifr mt-Cytb  3.21E−103 0.32028033 1 0.999 7.97E−99 UTM1 mt-Cytb Dak  1.12E−102 0.40580329 0.828 0.421 2.78E−98 UTM1 Dak Elovl6  4.00E−102 0.29994929 0.465 0.12 9.93E−98 UTM1 Elovl6 Nme1  9.03E−102 0.41494271 0.874 0.486 2.24E−97 UTM1 Nme1 Pklr  1.39E−101 0.33117616 0.631 0.227 3.45E−97 UTM1 Pklr Dnajb9  5.24E−101 0.27843915 0.463 0.122 1.30E−96 UTM1 Dnajb9 Oaz1  1.23E−100 0.39502814 0.935 0.65 3.06E−96 UTM1 Oaz1 Mbl2  4.21E−100 0.40599301 0.975 0.751 1.05E−95 UTM1 Mb12 Manf 2.64E−99 0.38367758 0.704 0.299 6.55E−95 UTM1 Manf Acat3 7.89E−99 0.40666807 0.848 0.467 1.96E−94 UTM1 Acat3 Etnppl 1.87E−98 0.42088555 0.875 0.461 4.64E−94 UTM1 Etnppl Plcxd2 1.39E−97 0.34692004 0.577 0.201 3.45E−93 UTM1 Plcxd2 Ostc 2.57E−97 0.36316755 0.604 0.225 6.39E−93 UTM1 Ostc Pnpla7 2.61E−97 0.36692003 0.831 0.432 6.47E−93 UTM1 Pnpla7 Hnmt 3.66E−97 0.26396164 0.404 0.092 9.08E−93 UTM1 Hnmt Eef1b2 9.52E−97 0.3987244 0.957 0.685 2.36E−92 UTM1 Eef1b2 Abca1 2.41E−96 0.35753365 0.631 0.24 5.98E−92 UTM1 Abca1 Fkbp3 9.55E−96 0.31527341 0.569 0.191 2.37E−91 UTM1 Fkbp3 Atp5a1 7.99E−95 0.35267049 0.993 0.843 1.98E−90 UTM1 Atp5a1 Aldh8a1 4.04E−93 0.384016 0.949 0.656 1.00E−88 UTM1 Aldh8a1 0610009D07Rik 5.21E−93 0.30838393 0.497 0.151 1.29E−88 UTM1 0610009D07Rik Abca8a 1.75E−92 0.27435964 0.505 0.155 4.33E−88 UTM1 Abca8a Scfd1 5.18E−91 0.29620765 0.548 0.188 1.29E−86 UTM1 Scfd1 Srebf1 7.07E−91 0.2732677 0.542 0.181 1.76E−86 UTM1 Srebf1 Tmed7 8.15E−91 0.31475685 0.616 0.233 2.02E−86 UTM1 Tmed7 Irf6 9.98E−91 0.28002315 0.414 0.107 2.48E−86 UTM1 Irf6 Nr2f6 6.62E−90 0.36238079 0.69 0.296 1.64E−85 UTM1 Nr2f6 Sigmar1 6.07E−89 0.37158458 0.765 0.38 1.51E−84 UTM1 Sigmar1 8430408G22Rik 7.17E−89 0.33485641 0.641 0.258 1.78E−84 UTM1 8430408G22Rik Sppl2a 4.27E−88 0.38180422 0.807 0.427 1.06E−83 UTM1 Sppl2a C8g 1.75E−87 0.34788408 0.997 0.863 4.34E−83 UTM1 C8g BC089597 2.97E−87 0.36854001 0.743 0.351 7.38E−83 UTM1 BC089597 Cmah 6.65E−87 0.29941181 0.725 0.326 1.65E−82 UTM1 Cmah Derl2 1.22E−86 0.34866072 0.753 0.363 3.02E−82 UTM1 Derl2 Lypla1 1.79E−86 0.35084069 0.794 0.402 4.44E−82 UTM1 Lypla1 Mettl9 2.28E−86 0.25341257 0.501 0.16 5.67E−82 UTM1 Mettl9 Dhcr24 3.92E−86 0.4030962 0.954 0.692 9.73E−82 UTM1 Dhcr24 Calm2 4.65E−86 0.320263 0.645 0.268 1.15E−81 UTM1 Calm2 Cnpy2 2.44E−85 0.36416686 0.816 0.431 6.06E−81 UTM1 Cnpy2 Commd6 3.71E−85 0.34118041 0.631 0.261 9.22E−81 UTM1 Commd6 Chchd3 4.45E−85 0.34865152 0.774 0.385 1.10E−80 UTM1 Chchd3 Hsd17b13 5.39E−85 0.37710065 0.939 0.634 1.34E−80 UTM1 Hsd17b13 Pdhb 1.32E−84 0.32631569 0.723 0.33 3.28E−80 UTM1 Pdhb Sar1a 1.56E−84 0.28167626 0.579 0.216 3.88E−80 UTM1 Sar1a Rbbp4 2.11E−84 0.28766422 0.542 0.197 5.25E−80 UTM1 Rbbp4 Cfh 2.26E−84 0.32111506 0.987 0.848 5.61E−80 UTM1 Cfh Hsd3b7 4.01E−84 0.38516037 0.961 0.71 9.96E−80 UTM1 Hsd3b7 Sdha 4.33E−84 0.37972281 0.938 0.645 1.08E−79 UTM1 Sdha Ghr 1.85E−83 0.35301973 0.971 0.76 4.59E−79 UTM1 Ghr Tmem126a 4.05E−83 0.30443005 0.552 0.203 1.01E−78 UTM1 Tmem126a Cyc1 5.59E−83 0.39233732 0.911 0.587 1.39E−78 UTM1 Cyc1 1110058L19Rik 2.22E−82 0.30158077 0.495 0.166 5.52E−78 UTM1 1110058L19Rik Sc4mol 2.65E−82 0.38075178 0.876 0.516 6.58E−78 UTM1 Sc4mol Ugt2a3 5.27E−82 0.37107252 0.947 0.68 1.31E−77 UTM1 Ugt2a3 Commd3 1.87E−81 0.30521803 0.705 0.314 4.64E−77 UTM1 Commd3 Atp6v0e 2.87E−81 0.28872503 0.59 0.23 7.13E−77 UTM1 Atp6v0e Spcs2 5.20E−81 0.34031177 0.759 0.382 1.29E−76 UTM1 Spcs2 Ldlr 6.47E−81 0.29459271 0.599 0.238 1.61E−76 UTM1 Ldlr Psmb1 7.06E−81 0.38386195 0.934 0.665 1.75E−76 UTM1 Psmb1 Mal2 1.03E−80 0.25266762 0.465 0.146 2.56E−76 UTM1 Mal2 Ctnnb1 2.43E−80 0.27274635 0.68 0.305 6.04E−76 UTM1 Ctnnb1 Tmem242 2.62E−80 0.25957867 0.531 0.188 6.50E−76 UTM1 Tmem242 Nsdhl 4.64E−80 0.31225962 0.639 0.27 1.15E−75 UTM1 Nsdhl Hsd3b3 1.28E−79 0.35671743 0.839 0.479 3.18E−75 UTM1 Hsd3b3 Dsg2 1.83E−79 0.32296016 0.721 0.343 4.54E−75 UTM1 Dsg2 Prdx1 2.34E−79 0.34215053 0.991 0.893 5.81E−75 UTM1 Prdx1 Ftcd 1.91E−78 0.36144063 0.907 0.575 4.75E−74 UTM1 Ftcd Adh5 2.70E−78 0.33120057 0.981 0.786 6.69E−74 UTM1 Adh5 Elovl3 2.80E−78 0.3774663 0.979 0.746 6.95E−74 UTM1 Elovl3 F2 3.01E−78 0.26845462 1 0.952 7.46E−74 UTM1 F2 Chchd2 6.51E−78 0.32338065 0.987 0.878 1.62E−73 UTM1 Chchd2 Bbox1 6.89E−78 0.35313715 0.789 0.419 1.71E−73 UTM1 Bbox1 1300002K09Rik 1.92E−77 0.31041035 0.768 0.377 4.76E−73 UTM1 1300002K09Rik Khk 2.02E−77 0.33758057 0.99 0.795 5.03E−73 UTM1 Khk Cpb2 2.12E−77 0.32650203 0.969 0.73 5.27E−73 UTM1 Cpb2 Psma1 1.03E−76 0.33310152 0.76 0.393 2.55E−72 UTM1 Psma1 Iah1 3.92E−76 0.35199549 0.838 0.491 9.74E−72 UTM1 Iah1 Gjb2 5.88E−76 0.32668553 0.815 0.442 1.46E−71 UTM1 Gjb2 Selenbp2 6.78E−76 0.28572648 0.997 0.905 1.68E−71 UTM1 Selenbp2 Agpat2 8.28E−76 0.33512398 0.872 0.513 2.06E−71 UTM1 Agpat2 Pvrl3 2.24E−75 0.27299335 0.516 0.19 5.56E−71 UTM1 Pvrl3 Slc25a15 4.50E−75 0.35215253 0.928 0.637 1.12E−70 UTM1 Slc25a15 Ndufs1 9.39E−75 0.27648065 0.719 0.34 2.33E−70 UTM1 Ndufs1 Tob1 1.26E−74 0.29859543 0.669 0.302 3.13E−70 UTM1 Tob1 Etnk1 1.33E−74 0.26868318 0.547 0.21 3.31E−70 UTM1 Etnk1 Cox7b 1.74E−74 0.43393382 0.99 0.818 4.32E−70 UTM1 Cox7b Ssr2 2.25E−74 0.30092095 0.698 0.33 5.58E−70 UTM1 Ssr2 Ssu72 2.77E−74 0.30608708 0.726 0.359 6.89E−70 UTM1 Ssu72 Ndufa4 4.03E−74 0.40135649 0.982 0.838 1.00E−69 UTM1 Ndufa4 Cox7a2 4.67E−74 0.41356585 0.932 0.705 1.16E−69 UTM1 Cox7a2 Ugt2b36 1.27E−73 0.3136071 0.997 0.894 3.16E−69 UTM1 Ugt2b36 Pqlc1 3.16E−73 0.25791546 0.587 0.239 7.85E−69 UTM1 Pqlc1 Rdh11 6.13E−73 0.28222183 0.571 0.23 1.52E−68 UTM1 Rdh11 Prlr 1.07E−72 0.25462979 0.531 0.201 2.65E−68 UTM1 Prlr Uqcrb 2.52E−72 0.35800773 0.843 0.532 6.27E−68 UTM1 Uqcrb Laptm4a 4.14E−72 0.30178581 0.817 0.462 1.03E−67 UTM1 Laptm4a Tram1 5.55E−72 0.2883247 0.752 0.383 1.38E−67 UTM1 Tram1 Ubl5 1.20E−71 0.28691562 0.609 0.262 2.98E−67 UTM1 Ubl5 Copb1 1.49E−71 0.28426912 0.663 0.303 3.69E−67 UTM1 Copb1 Deptor 1.50E−71 0.26550315 0.72 0.341 3.72E−67 UTM1 Deptor Rnf13 1.88E−71 0.29963446 0.752 0.39 4.67E−67 UTM1 Rnf13 Cyp51 3.23E−71 0.34072444 0.874 0.528 8.03E−67 UTM1 Cyp51 Uqcrfs1 4.97E−71 0.32365738 0.957 0.696 1.23E−66 UTM1 Uqcrfs1 Atg3 6.60E−71 0.28289063 0.73 0.358 1.64E−66 UTM1 Atg3 Apcs 7.87E−71 0.33098607 0.767 0.395 1.95E−66 UTM1 Apcs Apof 8.05E−71 0.27900656 0.986 0.85 2.00E−66 UTM1 Apof Arf4 3.11E−70 0.2516462 0.579 0.242 7.72E−66 UTM1 Arf4 Tpi1 4.79E−70 0.31291177 0.907 0.598 1.19E−65 UTM1 Tpi1 Sub1 9.00E−70 0.25980103 0.573 0.234 2.23E−65 UTM1 Sub1 Serpina12 3.66E−69 0.30327542 0.727 0.365 9.08E−65 UTM1 Serpina12 C8a 4.69E−69 0.28701937 0.983 0.835 1.17E−64 UTM1 C8a Dhcr7 5.00E−69 0.29409414 0.602 0.267 1.24E−64 UTM1 Dhcr7 F13b 1.25E−68 0.30662429 0.855 0.527 3.11E−64 UTM1 F13b Lyrm5 1.27E−68 0.28597928 0.619 0.277 3.15E−64 UTM1 Lyrm5 Ppp1r3b 1.35E−68 0.25254489 0.604 0.26 3.34E−64 UTM1 Ppp1r3b Ifitm3 1.73E−68 0.31398282 0.947 0.74 4.29E−64 UTM1 Ifitm3 Hsd17b2 2.17E−68 0.31035164 0.908 0.606 5.39E−64 UTM1 Hsd17b2 Rab10 2.97E−68 0.268356 0.647 0.289 7.37E−64 UTM1 Rab10 Bud31 3.01E−68 0.26276769 0.636 0.285 7.47E−64 UTM1 Bud31 Swi5 4.56E−68 0.29995649 0.736 0.375 1.13E−63 UTM1 Swi5 Emc7 4.89E−68 0.27676545 0.721 0.365 1.22E−63 UTM1 Emc7 Cltc 4.95E−68 0.25557028 0.641 0.291 1.23E−63 UTM1 Cltc Cct5 7.65E−68 0.27451127 0.782 0.421 1.90E−63 UTM1 Cct5 Atf4 1.20E−67 0.27512816 0.671 0.319 2.99E−63 UTM1 Atf4 Ndufb5 1.21E−67 0.33996987 0.826 0.497 3.01E−63 UTM1 Ndufb5 Gm5096 1.43E−67 0.26079 0.701 0.343 3.55E−63 UTM1 Gm5096 Perp 2.15E−67 0.26670351 0.688 0.333 5.34E−63 UTM1 Perp Rnf11 2.34E−67 0.2556776 0.717 0.346 5.81E−63 UTM1 Rnf11 Ndufa5 2.84E−67 0.29341766 0.791 0.446 7.06E−63 UTM1 Ndufa5 Serinc1 7.86E−67 0.30145323 0.84 0.478 1.95E−62 UTM1 Serinc1 Cyp2j5 2.08E−66 0.28302319 0.979 0.825 5.16E−62 UTM1 Cyp2j5 Fads1 2.27E−66 0.33006468 0.875 0.55 5.62E−62 UTM1 Fads1 Sucla2 3.33E−66 0.29066376 0.771 0.422 8.28E−62 UTM1 Sucla2 Pah 8.49E−66 0.28093156 0.981 0.843 2.11E−61 UTM1 Pah Sdhb 9.55E−66 0.31480778 0.951 0.715 2.37E−61 UTM1 Sdhb Cox4i1 1.20E−65 0.27616571 1 0.935 2.98E−61 UTM1 Cox4i1 Pipox 1.97E−65 0.2935053 0.776 0.427 4.90E−61 UTM1 Pipox Baat 4.65E−65 0.3059397 0.933 0.678 1.15E−60 UTM1 Baat Ctsl 5.37E−65 0.29836773 0.973 0.794 1.33E−60 UTM1 Ctsl Prkd3 2.21E−64 0.29616642 0.713 0.371 5.49E−60 UTM1 Prkd3 Akr1c20 1.15E−63 0.33238402 0.784 0.446 2.85E−59 UTM1 Akr1c20 Evi5 1.49E−63 0.26301342 0.713 0.357 3.70E−59 UTM1 Evi5 Mrps14 5.20E−63 0.26008108 0.569 0.246 1.29E−58 UTM1 Mrps14 Sfxn1 1.09E−62 0.265142 0.737 0.367 2.70E−58 UTM1 Sfxn1 Cyb5b 1.38E−62 0.32175064 0.911 0.624 3.43E−58 UTM1 Cyb5b Ccbl2 4.42E−62 0.28251976 0.801 0.451 1.10E−57 UTM1 Ccbl2 Qprt 7.81E−62 0.2899791 0.722 0.378 1.94E−57 UTM1 Qprt Ube2b 1.03E−61 0.27510318 0.704 0.356 2.57E−57 UTM1 Ube2b Kynu 1.28E−61 0.29239464 0.817 0.465 3.17E−57 UTM1 Kynu Timm8b 1.62E−61 0.29597925 0.747 0.406 4.03E−57 UTM1 Timm8b Glud1 2.91E−61 0.26489254 0.989 0.86 7.22E−57 UTM1 Glud1 Cnbp 6.36E−61 0.29562084 0.947 0.687 1.58E−56 UTM1 Cnbp Acss2 1.52E−60 0.30324766 0.808 0.449 3.78E−56 UTM1 Acss2 Cml2 2.02E−60 0.26434013 0.972 0.795 5.02E−56 UTM1 Cml2 Hal 5.96E−60 0.32620613 0.933 0.651 1.48E−55 UTM1 Hal Lgals9 1.05E−59 0.30869764 0.954 0.707 2.62E−55 UTM1 Lgals9 15-Sep 1.54E−59 0.32295173 0.896 0.578 3.82E−55 UTM1 15-Sep Iigp1 2.59E−59 0.25498285 0.938 0.664 6.43E−55 UTM1 Iigp1 Tlcd2 3.62E−59 0.28264137 0.765 0.413 8.98E−55 UTM1 Tlcd2 Aldh1a7 6.57E−59 0.29599695 0.854 0.529 1.63E−54 UTM1 Aldh1a7 Sar1b 1.79E−58 0.30909884 0.943 0.68 4.45E−54 UTM1 Sar1b Sdc2 2.74E−58 0.27931341 0.816 0.487 6.81E−54 UTM1 Sdc2 Ugt2b5 3.75E−58 0.25716502 0.999 0.937 9.32E−54 UTM1 Ugt2b5 Paics 9.16E−58 0.28698914 0.865 0.553 2.27E−53 UTM1 Paics Slc38a3 2.21E−57 0.28617356 0.971 0.797 5.48E−53 UTM1 Slc38a3 Zbtb20 2.34E−57 0.26498064 0.668 0.324 5.81E−53 UTM1 Zbtb20 Ghitm 3.39E−57 0.27864994 0.92 0.639 8.42E−53 UTM1 Ghitm Adk 7.84E−57 0.27373253 0.979 0.796 1.95E−52 UTM1 Adk Ssr3 4.83E−56 0.25203204 0.809 0.481 1.20E−51 UTM1 Ssr3 Pygl 5.88E−56 0.28584416 0.955 0.68 1.46E−51 UTM1 Pygl Etfa 4.41E−55 0.2569097 0.947 0.723 1.09E−50 UTM1 Etfa Csad 4.48E−55 0.34555095 0.902 0.659 1.11E−50 UTM1 Csad Mrpl12 6.08E−55 0.27496438 0.799 0.467 1.51E−50 UTM1 Mrpl12 Amdhd1 2.55E−54 0.28188607 0.87 0.549 6.33E−50 UTM1 Amdhd1 C1s 2.71E−54 0.25697751 0.897 0.582 6.73E−50 UTM1 C1s Psma2 4.37E−54 0.27369868 0.744 0.428 1.09E−49 UTM1 Psma2 S100a1 5.86E−54 0.29112411 0.858 0.555 1.45E−49 UTM1 S100a1 Tm7sf2 6.73E−54 0.26535039 0.736 0.404 1.67E−49 UTM1 Tm7sf2 Fdx1 1.81E−53 0.27825732 0.823 0.518 4.50E−49 UTM1 Fdx1 Adck3 4.36E−53 0.282871 0.948 0.665 1.08E−48 UTM1 Adck3 Hsd17b12 7.99E−53 0.25465919 0.85 0.539 1.98E−48 UTM1 Hsd17b12 Mcfd2 3.47E−52 0.26216867 0.857 0.529 8.63E−48 UTM1 Mcfd2 Ces1f 3.57E−52 0.27147075 0.955 0.744 8.87E−48 UTM1 Ces1f Hebp1 1.89E−49 0.26932242 0.913 0.662 4.70E−45 UTM1 Hebp1 Gnb2l1 3.81E−49 0.27040884 0.963 0.751 9.46E−45 UTM1 Gnb2l1 Ndufb8 7.67E−48 0.26808735 0.912 0.657 1.91E−43 UTM1 Ndufb8 Ugt3a2 1.72E−47 0.25614571 0.879 0.587 4.28E−43 UTM1 Ugt3a2 Tfr2 8.70E−47 0.25214071 0.832 0.526 2.16E−42 UTM1 Tfr2 Tmprss6 2.49E−44 0.25597646 0.914 0.643 6.18E−40 UTM1 Tmprss6 Cyp2b101 0 1.25971488 0.913 0.272 0 UTM5 Cyp2b10 Gm239351 0 1.13877874 0.999 0.871 0 UTM5 Gm23935 Ttr 0 0.46574445 1 0.999 0 UTM5 Ttr Apoe 0 0.43350247 1 1 0 UTM5 Apoe Hpd1  8.94E−267 0.55870766 0.999 0.96  2.22E−262 UTM5 Hpd Ankrd551  2.77E−259 1.04657324 0.972 0.494  6.87E−255 UTM5 Ankrd55 Cyb5  4.10E−251 0.54320014 1 0.971  1.02E−246 UTM5 Cyb5 Saa11  5.70E−245 0.91748275 0.905 0.484  1.42E−240 UTM5 Saa1 Gstm11  7.92E−243 0.76000515 0.998 0.89  1.97E−238 UTM5 Gstm1 Gstm31  3.48E−236 1.08145502 0.699 0.207  8.63E−232 UTM5 Gstm3 Mt11  5.28E−234 0.89508131 0.822 0.362  1.31E−229 UTM5 Mt1 Vtn  1.81E−219 0.48408458 1 0.97  4.50E−215 UTM5 Vtn Cyp2c291  2.49E−215 0.81028694 0.972 0.899  6.19E−211 UTM5 Cyp2c29 Cyp2a51  1.92E−211 1.0797726 0.822 0.361  4.76E−207 UTM5 Cyp2a5 Apoa21  1.29E−202 0.28295599 1 1  3.21E−198 UTM5 Apoa2 Apoa11  1.97E−200 0.28070646 1 1  4.90E−196 UTM5 Apoa1 Mt21  1.41E−195 0.72818605 0.636 0.168  3.50E−191 UTM5 Mt2 Hp1  6.85E−185 0.32448757 1 0.997  1.70E−180 UTM5 Hp Atp5h1  7.01E−179 0.67755519 0.867 0.547  1.74E−174 UTM5 Atp5h Gpx1  3.55E−154 0.28180291 1 0.997  8.81E−150 UTM5 Gpx1 Chchd101  4.15E−148 0.447182 0.991 0.91  1.03E−143 UTM5 Chchd10 Adh1  5.65E−144 0.39999808 0.999 0.932  1.40E−139 UTM5 Adh1 Aldh1a11  6.03E−143 0.4817687 0.997 0.926  1.50E−138 UTM5 Aldh1a1 Lrg11  3.27E−142 0.55473352 0.877 0.633  8.11E−138 UTM5 Lrg1 Gdf151  1.02E−137 0.61534668 0.58 0.216  2.54E−133 UTM5 Gdf15 Rnase41  2.68E−137 0.51253382 0.99 0.871  6.65E−133 UTM5 Rnase4 Hpx  4.74E−135 0.38094396 1 0.995  1.18E−130 UTM5 Hpx Apoc4  2.97E−132 0.37324314 0.999 0.966  7.37E−128 UTM5 Apoc4 Cyp2e11  1.64E−130 0.61429276 0.976 0.864  4.07E−126 UTM5 Cyp2e1 Serping11  4.00E−130 0.52201124 0.96 0.804  9.94E−126 UTM5 Serping1 Id31  1.50E−127 0.62698859 0.629 0.278  3.72E−123 UTM5 Id3 Cyp4a101  4.32E−127 0.56062409 0.829 0.531  1.07E−122 UTM5 Cyp4a10 Stard101  3.57E−123 0.34738438 0.999 0.944  8.86E−119 UTM5 Stard10 Cyp2d91  1.16E−120 0.36911806 0.999 0.93  2.88E−116 UTM5 Cyp2d9 Cyp1a21  3.03E−120 0.59697802 0.919 0.702  7.52E−116 UTM5 Cyp1a2 Cebpb1  1.84E−115 0.52562681 0.644 0.309  4.57E−111 UTM5 Cebpb Cyp2c501  3.03E−114 0.51306773 0.964 0.832  7.53E−110 UTM5 Cyp2c50 Serpina1a1  4.36E−113 0.29692434 1 0.984  1.08E−108 UTM5 Serpina1a Gstp11  2.22E−107 0.35098945 0.953 0.726  5.51E−103 UTM5 Gstp1 C4b1  3.15E−107 0.44347886 0.958 0.828  7.81E−103 UTM5 C4b Mug11  5.94E−104 0.29868649 0.999 0.982 1.47E−99 UTM5 Mug1 Ttc361  6.13E−102 0.35591693 0.992 0.919 1.52E−97 UTM5 Ttc36 Gadd45b1 1.96E−98 0.55034957 0.466 0.163 4.87E−94 UTM5 Gadd45b Gsta3 9.99E−98 0.37015533 0.999 0.925 2.48E−93 UTM5 Gsta3 1-Jun 9.07E−96 0.52377024 0.737 0.488 2.25E−91 UTM5 Jun 1100001G20Rik1 1.92E−93 0.30823546 0.999 0.97 4.76E−89 UTM5 1100001G20Rik Ces1c 3.51E−90 0.26725555 1 0.974 8.73E−86 UTM5 Ces1c Cyp27a1 8.39E−87 0.43363589 0.937 0.764 2.08E−82 UTM5 Cyp27a1 Fos1 4.46E−84 0.54575752 0.655 0.404 1.11E−79 UTM5 Fos Sephs21 6.09E−83 0.41975136 0.866 0.684 1.51E−78 UTM5 Sephs2 Itih4 3.62E−81 0.34372846 0.992 0.916 8.98E−77 UTM5 Itih4 Rps151 7.09E−81 0.37609074 0.685 0.414 1.76E−76 UTM5 Rps15 Pim31 7.78E−81 0.44118967 0.675 0.436 1.93E−76 UTM5 Pim3 Ephx11 1.29E−80 0.41078893 0.888 0.736 3.20E−76 UTM5 Ephx1 Clu 2.42E−80 0.31373997 0.995 0.93 6.01E−76 UTM5 Clu Por1 2.09E−78 0.35994138 0.813 0.575 5.19E−74 UTM5 Por Sult1d11 4.93E−78 0.45000439 0.806 0.594 1.22E−73 UTM5 Sult1d1 Junb1 1.08E−77 0.45123021 0.614 0.365 2.69E−73 UTM5 Junb Usmg51 2.84E−76 0.42129894 0.587 0.316 7.06E−72 UTM5 Usmg5 Cxcl1 6.62E−76 0.48969282 0.46 0.208 1.64E−71 UTM5 Cxcl1 mt-Nd41 5.60E−75 0.38334466 0.999 0.997 1.39E−70 UTM5 mt-Nd4 Ahcy1 1.92E−74 0.31198715 0.978 0.871 4.77E−70 UTM5 Ahcy Lcat1 3.72E−74 0.38055835 0.873 0.714 9.23E−70 UTM5 Lcat Fth1 9.59E−74 0.25419048 0.999 0.963 2.38E−69 UTM5 Fth1 Clpx 2.75E−73 0.41799583 0.9 0.698 6.82E−69 UTM5 Clpx Grhpr1 6.45E−72 0.37056505 0.868 0.705 1.60E−67 UTM5 Grhpr mt-Co11 1.16E−71 0.3699118 0.999 0.999 2.88E−67 UTM5 mt-Co1 Gchfr 9.17E−69 0.40305281 0.871 0.692 2.28E−64 UTM5 Gchfr Rpl351 3.15E−68 0.31190843 0.367 0.121 7.83E−64 UTM5 Rpl35 Cyp2c551 6.39E−68 0.42673384 0.382 0.142 1.59E−63 UTM5 Cyp2c55 Cox8a1 1.45E−67 0.37035824 0.735 0.537 3.60E−63 UTM5 Cox8a Eef1a11 1.55E−65 0.25671984 0.934 0.788 3.86E−61 UTM5 Eef1a1 Insig2 1.40E−64 0.36315872 0.907 0.739 3.47E−60 UTM5 Insig2 Ces2a1 6.29E−64 0.32781496 0.918 0.792 1.56E−59 UTM5 Ces2a Gulo1 7.25E−64 0.46673554 0.629 0.401 1.80E−59 UTM5 Gulo Haao 1.02E−62 0.34164895 0.952 0.794 2.53E−58 UTM5 Haao Cd302 1.20E−62 0.34750482 0.941 0.801 2.98E−58 UTM5 Cd302 Slc25a471 6.73E−62 0.30668037 0.976 0.891 1.67E−57 UTM5 Slc25a47 Mettl7b1 1.12E−60 0.29547032 0.939 0.819 2.79E−56 UTM5 Mettl7b Serpina3n1 3.29E−60 0.36591685 0.686 0.492 8.17E−56 UTM5 Serpina3n Saa21 5.98E−58 0.34882206 0.354 0.126 1.49E−53 UTM5 Saa2 Ehhadh1 2.11E−57 0.3315863 0.793 0.616 5.25E−53 UTM5 Ehhadh Ttpa 9.77E−57 0.30846742 0.941 0.816 2.43E−52 UTM5 Ttpa Tmem176b 1.05E−56 0.39429345 0.733 0.558 2.61E−52 UTM5 Tmem176b Cyp2c541 3.08E−56 0.35166996 0.856 0.688 7.65E−52 UTM5 Cyp2c54 Creg1 5.60E−54 0.27676691 0.977 0.888 1.39E−49 UTM5 Creg1 Blvrb1 5.56E−53 0.35628811 0.671 0.486 1.38E−48 UTM5 Blvrb mt-Nd51 3.78E−52 0.30458553 0.997 0.994 9.39E−48 UTM5 mt-Nd5 Ang 4.85E−52 0.34485878 0.791 0.61 1.20E−47 UTM5 Ang Pcbd1 7.00E−52 0.30897079 0.926 0.772 1.74E−47 UTM5 Pcbd1 Gstm4 8.03E−52 0.39950266 0.557 0.361 1.99E−47 UTM5 Gstm4 Hmgcl 1.77E−51 0.34120969 0.814 0.667 4.38E−47 UTM5 Hmgcl Fgl11 2.73E−51 0.28479212 0.866 0.725 6.78E−47 UTM5 Fgl1 Sqstm11 4.59E−51 0.30323927 0.891 0.743 1.14E−46 UTM5 Sqstm1 Rarres2 2.72E−48 0.270449 0.969 0.858 6.75E−44 UTM5 Rarres2 Cyp2c371 3.23E−48 0.35466642 0.725 0.523 8.02E−44 UTM5 Cyp2c37 Ier2 4.25E−47 0.36177787 0.595 0.413 1.05E−42 UTM5 Ier2 Ndufs8 3.46E−46 0.32706621 0.704 0.537 8.59E−42 UTM5 Ndufs8 Abcc31 1.11E−45 0.33711807 0.643 0.467 2.76E−41 UTM5 Abcc3 Slc22a11 1.81E−45 0.34693238 0.824 0.691 4.49E−41 UTM5 Slc22a1 Gstt31 6.29E−45 0.28628594 0.403 0.201 1.56E−40 UTM5 Gstt3 Hrg 1.33E−44 0.29365973 0.911 0.773 3.29E−40 UTM5 Hrg Rnf125 5.51E−44 0.35260939 0.59 0.422 1.37E−39 UTM5 Rnf125 F10 7.41E−44 0.26087857 0.958 0.848 1.84E−39 UTM5 F10 Decr21 1.03E−43 0.26539891 0.726 0.567 2.56E−39 UTM5 Decr2 Nr1i31 1.14E−43 0.30480484 0.495 0.291 2.82E−39 UTM5 Nr1i3 Arrdc3 6.96E−43 0.30193418 0.317 0.136 1.73E−38 UTM5 Arrdc3 Lect21 7.92E−43 0.32510938 0.526 0.332 1.97E−38 UTM5 Lect2 4931406C07Rik1 6.05E−42 0.26266358 0.822 0.694 1.50E−37 UTM5 4931406C07Rik Zfp36 3.34E−40 0.34031672 0.616 0.453 8.29E−36 UTM5 Zfp36 Gstm2 4.91E−40 0.30094499 0.263 0.101 1.22E−35 UTM5 Gstm2 Ndufa7 1.62E−39 0.28033658 0.804 0.655 4.01E−35 UTM5 Ndufa7 Selenbp1 1.24E−38 0.31122695 0.779 0.64 3.07E−34 UTM5 Selenbp1 Akr1c14 1.49E−38 0.29991907 0.796 0.642 3.70E−34 UTM5 Akr1c14 Cdkn1a 1.01E−37 0.31716116 0.288 0.127 2.51E−33 UTM5 Cdkn1a Cyp4f151 1.32E−37 0.28293592 0.529 0.355 3.27E−33 UTM5 Cyp4f15 Slc27a5 3.39E−37 0.25311303 0.967 0.839 8.41E−33 UTM5 Slc27a5 Grn1 3.92E−37 0.31937969 0.49 0.327 9.74E−33 UTM5 Grn Jund1 1.07E−36 0.26166892 0.402 0.227 2.66E−32 UTM5 Jund Papss2 4.28E−36 0.32662518 0.592 0.446 1.06E−31 UTM5 Papss2 Tmem14c 1.87E−35 0.27112198 0.668 0.524 4.66E−31 UTM5 Tmem14c Serpinf2 9.46E−35 0.25152649 0.932 0.778 2.35E−30 UTM5 Serpinf2 Atf3 1.61E−34 0.26673538 0.268 0.115 3.99E−30 UTM5 Atf3 Car5a 1.23E−33 0.27823285 0.426 0.261 3.05E−29 UTM5 Car5a Aldh3a21 1.96E−33 0.28055406 0.627 0.457 4.87E−29 UTM5 Aldh3a2 Gclc 2.02E−33 0.27548506 0.81 0.652 5.02E−29 UTM5 Gclc Oaf 2.11E−33 0.26638374 0.875 0.736 5.23E−29 UTM5 Oaf Apoc2 3.74E−33 0.26484153 0.874 0.749 9.28E−29 UTM5 Apoc2 Gpld1 4.73E−33 0.27600756 0.656 0.519 1.17E−28 UTM5 Gpld1 Fcgrt 1.15E−32 0.26729682 0.67 0.548 2.85E−28 UTM5 Fcgrt Os91 2.32E−32 0.27254554 0.74 0.607 5.75E−28 UTM5 Os9 Egr1 4.39E−31 0.30443562 0.534 0.383 1.09E−26 UTM5 Egr1 AI182371 3.39E−30 0.25241508 0.7 0.565 8.43E−26 UTM5 AI182371 Dcxr 1.15E−29 0.25873551 0.702 0.579 2.87E−25 UTM5 Dcxr Mvd 3.99E−24 0.26099975 0.344 0.214 9.91E−20 UTM5 Mvd Hsbp1 6.04E−23 0.25129426 0.56 0.453 1.50E−18 UTM5 Hsbp1 Gstm6 2.26E−19 0.25216132 0.418 0.303 5.61E−15 UTM5 Gstm6 Mup62 0 2.1978265 1 0.99 0 UTM6 Mup6 Mup192 0 1.93347001 1 1 0 UTM6 Mup19 Mup52 0 1.84833854 0.956 0.804 0 UTM6 Mup5 Mup92 0 1.72069868 1 0.969 0 UTM6 Mup9 Mup42 0 1.70689156 0.977 0.875 0 UTM6 Mup4 Mup182 0 1.70527221 1 0.996 0 UTM6 Mup18 Mup72 0 1.47233248 1 0.997 0 UTM6 Mup7 Mup171  6.34E−294 1.18231635 1 1  1.57E−289 UTM6 Mup17 Mup111  1.10E−284 0.88902183 1 1  2.72E−280 UTM6 Mup11 Mup152  4.14E−269 1.73856185 0.882 0.538  1.03E−264 UTM6 Mup15 Zfp683  1.40E−265 1.15363136 0.464 0.013  3.48E−261 UTM6 Zfp683 mmu-mir-62362  2.75E−253 1.74996425 0.937 0.807  6.84E−249 UTM6 mmu-mir-6236 Mup202  2.90E−223 0.88182043 1 1  7.21E−219 UTM6 Mup20 Mup112  2.80E−219 1.50547218 0.832 0.51  6.96E−215 UTM6 Mup1 Mup102  1.09E−218 1.51308329 0.855 0.644  2.70E−214 UTM6 Mup10 mt-Co21  1.01E−209 1.54504766 0.85 0.563  2.51E−205 UTM6 mt-Co2 Mup162  3.06E−209 1.07242857 0.941 0.932  7.59E−205 UTM6 Mup16 Malat11  1.37E−207 1.32741509 0.909 0.742  3.41E−203 UTM6 Malat1 Mup141  3.97E−190 1.32922546 0.817 0.556  9.87E−186 UTM6 Mup14 Mup212  2.78E−182 0.86449671 0.943 0.924  6.90E−178 UTM6 Mup21 Mup82  3.15E−165 1.37369891 0.668 0.285  7.83E−161 UTM6 Mup8 Lars21  9.42E−162 0.76849968 0.99 0.996  2.34E−157 UTM6 Lars2 Mup122  4.34E−151 0.93855833 0.875 0.855  1.08E−146 UTM6 Mup12 mt-Atp62  2.51E−137 1.29404948 0.686 0.383  6.23E−133 UTM6 mt-Atp6 mt-Co31  4.13E−117 1.09991599 0.762 0.555  1.03E−112 UTM6 mt-Co3 Mup23  1.11E−113 1.13035871 0.616 0.326  2.75E−109 UTM6 Mup2 Gm205942  7.76E−113 1.04926452 0.549 0.219  1.93E−108 UTM6 Gm20594 Gm269241  3.84E−107 0.56665866 1 1  9.53E−103 UTM6 Gm26924 Gm137751 9.06E−88 0.83647132 0.772 0.757 2.25E−83 UTM6 Gm13775 Gstp12 9.87E−87 0.68055321 0.871 0.807 2.45E−82 UTM6 Gstp1 Rpl412 2.55E−78 0.95632944 0.482 0.218 6.34E−74 UTM6 Rpl41 Scp21 5.17E−76 0.42678693 0.952 0.996 1.28E−71 UTM6 Scp2 mt-Rnr1 3.95E−68 0.42177683 1 1 9.81E−64 UTM6 mt-Rnr1 Sparcl1 6.00E−68 0.60925972 0.308 0.085 1.49E−63 UTM6 Sparcl1 Ftl12 1.01E−56 0.86494473 0.537 0.371 2.51E−52 UTM6 Ftl1 Hamp1 1.07E−54 0.53431054 0.835 0.899 2.65E−50 UTM6 Hamp Gm155641 6.11E−52 0.49223563 0.9 0.972 1.52E−47 UTM6 Gm15564 Gm242451 6.15E−44 0.67966077 0.36 0.171 1.53E−39 UTM6 Gm24245 Cyp3a44 8.24E−41 0.5893919 0.323 0.142 2.05E−36 UTM6 Cyp3a44 Gm4076 2.95E−36 0.61348099 0.314 0.146 7.33E−32 UTM6 Gm4076 Mup131 1.47E−32 0.63253389 0.59 0.533 3.65E−28 UTM6 Mup13 mt-Nd52 6.68E−32 0.37550761 0.988 0.997 1.66E−27 UTM6 mt-Nd5 Hsp90b11 8.04E−29 0.37916528 0.888 0.972 2.00E−24 UTM6 Hsp90b1 Eef1a12 7.93E−27 0.42249546 0.746 0.881 1.97E−22 UTM6 Eef1a1 Cyp2e12 5.38E−26 0.39331803 0.897 0.915 1.34E−21 UTM6 Cyp2e1 mt-Nd2 6.69E−23 0.29590227 0.996 1 1.66E−18 UTM6 mt-Nd2 Rn7sk 3.38E−22 0.53767783 0.283 0.157 8.38E−18 UTM6 Rn7sk Cfb1 1.06E−20 0.51119164 0.564 0.57 2.63E−16 UTM6 Cfb Ubb1 1.76E−20 0.62082198 0.485 0.439 4.36E−16 UTM6 Ubb Rps181 5.88E−18 0.58975018 0.555 0.585 1.46E−13 UTM6 Rps18 Acaa1a1 1.88E−15 0.47992175 0.602 0.702 4.66E−11 UTM6 Acaa1a Acsl1 1.45E−13 0.29198038 0.812 0.958 3.59E−09 UTM6 Acsl1 Rplp1 1.81E−11 0.38988375 0.644 0.791 4.50E−07 UTM6 Rplp1 Rps3a11 2.43E−11 0.51647276 0.373 0.324 6.03E−07 UTM6 Rps3a1 Rps22 1.83E−10 0.39471423 0.638 0.792 4.55E−06 UTM6 Rps2 mt-Nd61 6.18E−10 0.53191088 0.531 0.591 1.53E−05 UTM6 mt-Nd6 Rps191 7.08E−10 0.56897855 0.46 0.478 1.76E−05 UTM6 Rps19 Rpl371 3.50E−09 0.44536423 0.28 0.221 8.70E−05 UTM6 Rpl37 Gm98431 4.44E−09 0.49576113 0.333 0.289 0.00011029 UTM6 Gm9843 Cyp7b11 6.85E−08 0.34003655 0.65 0.788 0.00170044 UTM6 Cyp7b1 Txnip1 2.08E−07 0.46854072 0.328 0.288 0.00515553 UTM6 Txnip Acadm 3.44E−07 0.41172686 0.593 0.768 0.00854147 UTM6 Acadm Por2 4.81E−07 0.40526153 0.586 0.702 0.01194371 UTM6 Por Rpl35a 7.34E−07 0.50694911 0.373 0.364 0.01823153 UTM6 Rpl35a Cyp4a141 9.89E−07 0.49263055 0.419 0.434 0.02454877 UTM6 Cyp4a14 Rpl261 1.34E−06 0.40870741 0.485 0.544 0.03335525 UTM6 Rpl26 St3gal51 1.55E−06 0.47782408 0.46 0.499 0.03844786 UTM6 St3gal5 Plin2 8.88E−06 0.39991811 0.584 0.753 0.22063007 UTM6 Plin2 Atp5e1 9.71E−05 0.30778372 0.69 0.875 1 UTM6 Atp5e Rpl71 9.76E−05 0.3671681 0.257 0.226 1 UTM6 Rpl7 Rps91 0.00010397 0.39135344 0.557 0.71 1 UTM6 Rps9 Gm102501 0.00071118 0.35509478 0.266 0.246 1 UTM6 Gm10250 Epb4.1 0.00164191 0.26962248 0.224 0.328 1 UTM6 Epb4.1 Rpl36al1 0.00170775 0.40245344 0.472 0.575 1 UTM6 Rpl36al Pdap1 0.00208461 0.26844074 0.239 0.354 1 UTM6 Pdap1 Cox6b1 0.00306562 0.26517687 0.656 0.855 1 UTM6 Cox6b1 Alas11 0.00687451 0.28080817 0.6 0.767 1 UTM6 Alas1 Rps201 0.00787049 0.37390189 0.49 0.613 1 UTM6 Rps20 Eif1 0.00888028 0.36530092 0.409 0.481 1 UTM6 Eif1

While hepatocytes from each untreated mouse clustered independently, the injury samples grouped by time point and injury type, rather than mouse of origin, indicating that the transcriptional response to injury causes individual hepatocytes to become more similar to one another. To confirm that this clustering captures biological, rather than technical, variation, Applicants performed differential expression to identify genes unique to each cluster. Clusters were defined by many genes related to liver function, injury response, and oxidative stress (FIG. 18D, see, e.g. Tables 2-5c), and technical gradients led to variation within, rather than across, clusters (nGene, nUMI; FIG. 25A-25H). Regression over technical variables (i.e., number of genes) largely removed these technical gradients, but preserved other, biologically important signals; removal of PC1, which captured technical effects, similarly resulted in a reduction of technical signals while preserving key biological ones. Since regression changed very little, other than downweighting technical differences in cell quality, and the biological signals on which this work focuses were robust to regression, Applicants opted to use the non-regressed dataset in our downstream analysis to avoid possible introduction of artificial variation.

APAP injury resulted in pericentral necrosis after 6 hrs as demonstrated by histological analysis (hereafter A6; FIG. 18B, 18C). Hepatocytes scoring high for a pericentral hepatocyte signature (PCHSig) were absent at 6 hours (hrs) post-APAP (A6, FIG. 18F). Surprisingly, at 24 hrs post-APAP, the pericentral hepatocyte expression signature returned (A24, FIG. 18F), despite histology showing persistent pericentral necrosis (A24, FIG. 18B, 18C). In particular, expression of two typically pericentrally restricted genes—Cyp2e1, responsible for metabolizing APAP, and Glu1, which assimilates ammonia into glutamine—was maintained, or returned, following pericentral injury. For example, Cyp2e1+ hepatocytes decreased from 67% (Untreated, UT) to 5% (A6), but returned back to 46% by 24 hrs with no significant change in Glu1+ hepatocytes at any time point. These results suggest the intriguing possibility of compensatory expression of pericentral genes by non-pericentral hepatocytes.

TABLE 14a APAP vs. UT ID p_val avg_logFC pct.1 pct.2 p_val_adj Mat1a 0 0.750044423 0.983 0.966 0 Sepp1 0 0.345459872 1 1 0 Mup3 0 −0.542484173 0.999 1 0 mt-Rnr2 0 −0.545826779 1 1 0 mt-Nd1 0 −0.759986171 0.978 1 0 mt-Nd5 0 −0.779679711 0.942 0.995 0 Selenbp2 0 −0.830430695 0.751 0.937 0 mt-Nd2 0 −0.832515437 0.978 0.999 0 Mup21 0 −0.872348794 0.702 0.929 0 mt-Cytb 0 −0.877546618 0.971 0.999 0 mt-Co1 0 −0.921896864 0.977 0.999 0 Gm13775 0 −1.061267629 0.306 0.761 0 mt-Co2 0 −1.077728564 0.157 0.629 0 mt-Nd4 0 −1.115678214 0.942 0.998 0 Mup16 0 −1.12499966 0.594 0.934 0 Mup15 0 −1.259561807 0.166 0.617 0 Mup5 0 −1.341986627 0.541 0.839 0 Mup18 0 −1.638566323 0.838 0.997 0 Mup11 0 −1.728428444 0.84 1 0 Mup19 0 −1.785867292 0.916 1 0 Mup6 0 −1.881843585 0.804 0.992 0 Mup9 0 −1.914490248 0.594 0.976 0 Mup17 0 −2.016622219 0.947 1 0 Cyp4a14  1.20E−300 1.281150046 0.714 0.431  2.97E−296 mt-Co3  1.54E−290 −0.958403256 0.198 0.603  3.82E−286 Serpina1e  1.35E−287 −0.468116476 0.99 0.999  3.36E−283 Gm15564  1.15E−262 1.171130141 0.981 0.956  2.85E−258 Akr1c6  4.68E−230 −0.504664681 0.92 0.971  1.16E−225 Ankrd55  6.63E−225 −1.230858809 0.451 0.696  1.65E−220 Lars2  2.20E−221 1.06892618 0.997 0.994  5.46E−217 Gm26924  1.56E−214 0.85076884 1 1  3.86E−210 Mup4  8.62E−211 −1.000765415 0.716 0.898  2.14E−206 mt-Rnr1  1.37E−205 −0.353829755 1 1  3.40E−201 C3  9.78E−200 0.350190783 0.997 0.99  2.43E−195 Fabp1  3.44E−187 −0.30775699 0.992 1  8.54E−183 Hspa5  2.31E−180 0.404849756 0.971 0.944  5.73E−176 Cp  9.33E−179 0.375775919 0.965 0.943  2.32E−174 Elovl3  5.11E−177 −0.522135473 0.65 0.827  1.27E−172 Gsta3  4.62E−168 −0.404911812 0.958 0.956  1.15E−163 Mup7  2.96E−167 −0.601531682 0.937 0.998  7.35E−163 n-R5-8s1  8.50E−167 0.696528218 0.268 0.031  2.11E−162 Nudt7  3.51E−163 −0.6192372 0.691 0.83  8.71E−159 Serpina1a  1.94E−157 −0.33473551 0.96 0.991  4.81E−153 Uqcrq  7.40E−157 −0.410137125 0.902 0.951  1.84E−152 Hnf4a  6.16E−155 0.453812022 0.876 0.743  1.53E−150 Ttpa  9.28E−150 0.393179802 0.916 0.869  2.30E−145 Car3  2.61E−147 −0.376245944 0.956 0.974  6.47E−143 Angptl3  1.63E−146 0.414020213 0.961 0.944  4.04E−142 Serpina3m  1.77E−141 0.459745121 0.836 0.722  4.39E−137 Fga  3.27E−140 0.433534845 0.996 0.997  8.13E−136 Fn1  2.00E−138 0.473677819 0.912 0.821  4.95E−134 Scd1  4.70E−138 0.512243564 0.969 0.901  1.17E−133 Ces3a  1.36E−137 −0.317352764 0.93 0.967  3.38E−133 Mfsd2a  3.04E−137 0.448359194 0.413 0.148  7.55E−133 Snord118  3.94E−137 0.470651684 0.531 0.248  9.78E−133 Mup8  1.52E−136 −0.726763962 0.13 0.373  3.77E−132 Ndrg2  9.66E−134 0.28448062 0.956 0.939  2.40E−129 Igfbp4  6.05E−133 0.31482773 0.919 0.866  1.50E−128 Adh1  1.12E−132 −0.31221001 0.941 0.96  2.79E−128 Serpina3n  3.83E−132 0.449619441 0.76 0.574  9.50E−128 Hp  8.34E−132 0.260394974 0.998 0.999  2.07E−127 Prdx1  2.41E−131 −0.349862194 0.878 0.927  5.99E−127 Gm24601  3.54E−131 0.4961857 0.198 0.015  8.80E−127 Gstp1  4.61E−130 −0.608807368 0.702 0.822  1.14E−125 Hsd3b7  3.94E−128 −0.450130172 0.693 0.798  9.79E−124 Grip2  8.48E−125 0.379665448 0.158 0.002  2.11E−120 Apoc2  7.71E−123 0.510711685 0.851 0.802  1.91E−118 Cyp4a10  1.33E−120 0.715856279 0.727 0.657  3.31E−116 Acaa1b  1.79E−119 −0.315795941 0.883 0.969  4.44E−115 Fgb  2.98E−118 0.390519359 0.999 1  7.40E−114 Mup20  2.74E−117 −0.372499315 0.992 1  6.81E−113 Mup13  3.18E−117 −0.624965563 0.351 0.546  7.90E−113 Aldob  1.56E−114 0.257594907 0.997 0.996  3.87E−110 Lpin2  1.59E−114 0.398387997 0.79 0.597  3.95E−110 Rsp14  1.62E−111 −0.336423845 0.856 0.917  4.03E−107 Sephs2  1.60E−110 0.428627671 0.865 0.761  3.97E−106 Lrg1  1.71E−110 0.347811428 0.861 0.736  4.24E−106 Slco1a4  2.27E−110 0.382614872 0.484 0.238  5.64E−106 Pabpc1  4.89E−109 0.373452962 0.75 0.592  1.21E−104 Cyb5  5.75E−109 −0.284450423 0.972 0.983  1.43E−104 P4hb  2.06E−108 0.258583074 0.958 0.941  5.13E−104 2810007J24Rik  3.82E−107 −0.287090402 0.909 0.943  9.49E−103 Apoa4  1.21E−105 0.598398872 0.574 0.339  3.01E−101 Dhcr24  1.89E−105 0.362875988 0.883 0.783  4.69E−101 Grn  1.70E−104 0.369164433 0.62 0.396  4.21E−100 Hsd3b5  2.16E−104 −0.471194244 0.367 0.587  5.37E−100 Mup12  3.61E−104 −0.371327569 0.665 0.86  8.97E−100 St3gal5  4.68E−104 0.387569967 0.695 0.49 1.16E−99 Sparcl1  7.00E−103 −0.253616986 0 0.136 1.74E−98 Wbp1l  1.55E−102 0.366182386 0.768 0.606 3.84E−98 Hrg  7.10E−102 0.321041129 0.88 0.831 1.76E−97 Sult1a1 1.38E−97 0.365154041 0.799 0.707 3.42E−93 Fgg 1.52E−96 0.339113048 0.997 0.991 3.78E−92 Cox4i1 2.61E−94 −0.262749367 0.941 0.958 6.48E−90 Gyk 2.78E−94 0.314409774 0.583 0.35 6.90E−90 Oaz1 5.51E−93 −0.394430119 0.651 0.75 1.37E−88 Eef2 2.12E−92 0.291153401 0.928 0.873 5.27E−88 Tmem205 1.10E−91 −0.295263774 0.877 0.934 2.74E−87 Man2a1 2.30E−91 0.340428532 0.742 0.583 5.70E−87 Itih3 2.87E−91 0.330302128 0.937 0.89 7.12E−87 Itih4 2.97E−91 0.282959368 0.97 0.948 7.36E−87 Gclc 6.76E−90 0.670994545 0.839 0.718 1.68E−85 Eif4g2 1.91E−89 0.340677509 0.824 0.678 4.75E−85 Il1r1 7.47E−88 0.363254586 0.39 0.167 1.85E−83 Tm4sf4 1.42E−87 0.275958137 0.493 0.256 3.54E−83 Chchd10 8.26E−87 0.383325007 0.925 0.944 2.05E−82 Tmed5 4.26E−86 0.302739481 0.689 0.492 1.06E−81 Retsat 4.94E−86 0.412599616 0.87 0.83 1.23E−81 Lpgat1 6.97E−85 0.353866188 0.693 0.502 1.73E−80 Serpina3c 4.51E−84 −0.425256202 0.208 0.385 1.12E−79 Ugt2b1 1.86E−83 −0.30063164 0.817 0.871 4.62E−79 Ddx21 1.16E−81 0.257603416 0.447 0.22 2.87E−77 Trp53inp1 6.93E−81 0.397717854 0.526 0.308 1.72E−76 Rps2 3.51E−80 −0.379370911 0.637 0.757 8.73E−76 Myh9 5.00E−80 0.450738112 0.531 0.318 1.24E−75 Itih2 7.80E−80 0.268155336 0.942 0.884 1.94E−75 Gm23935 9.33E−80 0.570137239 0.954 0.925 2.32E−75 Bach1 1.69E−79 0.261285488 0.356 0.151 4.19E−75 Asl 5.93E−79 0.337397732 0.859 0.787 1.47E−74 Agt 1.51E−78 0.300654386 0.859 0.817 3.75E−74 Slc4a4 3.95E−78 0.282733417 0.558 0.336 9.81E−74 Slc7a2 5.73E−78 0.333442671 0.829 0.735 1.42E−73 Inmt 1.03E−77 −0.366227618 0.871 0.884 2.55E−73 Fmo5 4.81E−77 0.254462826 0.914 0.837 1.19E−72 Aldh9a1 9.61E−75 0.271493861 0.836 0.763 2.39E−70 Dnajc3 2.25E−74 0.270821541 0.86 0.772 5.60E−70 Csde1 4.00E−74 0.273863255 0.749 0.577 9.94E−70 Agpat6 1.55E−73 0.27062679 0.695 0.517 3.86E−69 Cox6c 1.98E−73 −0.343178548 0.808 0.884 4.92E−69 Hmgcs2 7.75E−73 0.310476909 0.974 0.986 1.92E−68 Ndufb11 7.98E−73 −0.352187855 0.637 0.735 1.98E−68 Cdo1 9.77E−73 0.266520006 0.964 0.96 2.43E−68 Cyp7b1 1.18E−72 −0.351246722 0.654 0.757 2.92E−68 Cyp1a2 2.21E−72 −0.303458132 0.621 0.794 5.49E−68 Epb4.1 3.08E−72 0.256691619 0.527 0.304 7.65E−68 Sh3glb1 9.12E−72 0.252065411 0.47 0.258 2.27E−67 C8g 9.19E−72 −0.258246671 0.859 0.91 2.28E−67 Rdx 1.14E−71 0.282860025 0.775 0.63 2.82E−67 Eif5 1.43E−71 0.259766522 0.84 0.74 3.55E−67 Iigp1 1.79E−71 0.34482133 0.851 0.759 4.45E−67 Arhgap5 3.14E−71 0.287540755 0.647 0.454 7.79E−67 D17Wsu92e 3.82E−71 0.280932562 0.736 0.588 9.48E−67 Atp2a2 5.01E−71 0.303121987 0.666 0.495 1.24E−66 Uroc1 1.56E−70 0.313479852 0.74 0.615 3.86E−66 Cpt1a 2.48E−70 0.285036071 0.775 0.651 6.15E−66 Slc39a14 2.80E−70 0.355950632 0.552 0.343 6.96E−66 Pigr 3.30E−70 0.274660157 0.952 0.947 8.21E−66 Lifr 5.26E−70 −0.353193545 0.608 0.694 1.31E−65 Hamp 1.12E−69 −0.274177459 0.718 0.884 2.79E−65 Etf1 1.81E−69 0.275594116 0.61 0.409 4.48E−65 Tnfrsf12a 2.18E−69 0.258809369 0.193 0.052 5.42E−65 Abcb4 5.90E−69 0.275923839 0.78 0.675 1.46E−64 Ranbp2 2.49E−68 0.256706494 0.555 0.338 6.17E−64 Mbnl1 3.62E−68 0.250989808 0.511 0.297 9.00E−64 Zfp91 1.31E−67 0.261914675 0.666 0.492 3.26E−63 Rora 1.63E−67 0.285339115 0.547 0.341 4.04E−63 Tgoln1 3.36E−67 0.267654107 0.713 0.575 8.35E−63 Hsd17b13 4.56E−67 0.443731877 0.798 0.74 1.13E−62 Cfhr2 1.47E−66 −0.329112182 0.854 0.868 3.64E−62 Elovl2 2.70E−66 0.275127171 0.831 0.699 6.69E−62 Gm2a 4.22E−66 0.281407096 0.599 0.427 1.05E−61 Dennd5b 4.24E−66 0.256205947 0.55 0.334 1.05E−61 Abca6 6.79E−66 0.26370262 0.679 0.507 1.69E−61 Hbb-bs 9.29E−66 1.33215306 0.125 0.018 2.31E−61 Mia3 1.03E−65 0.255732645 0.749 0.61 2.57E−61 Pten 1.04E−65 0.264976186 0.645 0.458 2.58E−61 Txnrd1 1.49E−65 0.44747429 0.64 0.441 3.70E−61 Sdhc 1.53E−65 0.260461296 0.738 0.63 3.81E−61 Herpud1 2.81E−65 0.297286245 0.842 0.803 6.98E−61 Ddx3x 8.72E−64 0.275330763 0.689 0.513 2.17E−59 Gfra1 2.53E−63 0.253571589 0.676 0.498 6.29E−59 Eif1a 4.82E−63 0.266737555 0.492 0.289 1.20E−58 Fgl1 1.26E−62 0.361141465 0.861 0.784 3.12E−58 Ell2 5.11E−62 0.257245989 0.609 0.416 1.27E−57 Usp9x 1.80E−61 0.254069319 0.503 0.299 4.47E−57 Mup14 2.61E−61 −0.524421073 0.469 0.616 6.49E−57 Lipa 3.53E−61 0.257743912 0.73 0.61 8.77E−57 Srxn1 3.87E−61 0.563990466 0.369 0.189 9.60E−57 Sec61a1 4.35E−61 0.264849626 0.642 0.476 1.08E−56 Reep6 5.73E−61 0.289187421 0.837 0.794 1.42E−56 Bche 9.44E−61 0.256643093 0.562 0.369 2.34E−56 Aplp2 1.24E−60 0.263796183 0.759 0.625 3.09E−56 Slc40a1 1.54E−60 0.276808969 0.517 0.328 3.84E−56 Aadac 2.88E−59 −0.324280061 0.849 0.86 7.15E−55 Kif1b 3.89E−59 0.263987547 0.629 0.435 9.66E−55 Arhgef12 4.79E−59 0.278318571 0.597 0.408 1.19E−54 Atp1a1 3.90E−58 0.287145639 0.623 0.457 9.68E−54 Keg1 4.07E−58 −0.385687903 0.441 0.545 1.01E−53 Gm4076 4.99E−58 −0.269795145 0.057 0.184 1.24E−53 Cyp2a5 7.24E−58 −0.327337224 0.388 0.555 1.80E−53 Fam134b 2.09E−57 0.298654652 0.589 0.405 5.19E−53 Chchd2 3.96E−57 −0.257495549 0.874 0.916 9.83E−53 Creld2 4.34E−57 0.262631686 0.487 0.296 1.08E−52 Hyou1 5.77E−57 0.365752306 0.561 0.385 1.43E−52 Hmox1 9.91E−57 0.329838257 0.108 0.016 2.46E−52 Ces3b 1.20E−56 −0.283988668 0.727 0.787 2.98E−52 Ttc39c 4.98E−56 −0.318694789 0.573 0.642 1.24E−51 Ube2r2 6.52E−56 0.260699825 0.655 0.525 1.62E−51 Picalm 8.44E−55 0.266596403 0.558 0.376 2.10E−50 Cite 1.40E−54 0.30770172 0.602 0.414 3.47E−50 Slc25a47 1.66E−54 0.309555605 0.927 0.927 4.13E−50 Lrrc58 1.38E−53 0.299758126 0.542 0.359 3.42E−49 Brd2 1.64E−53 0.285550428 0.59 0.408 4.07E−49 Gstm3 2.30E−53 −0.47361305 0.269 0.414 5.70E−49 F5 7.46E−53 0.260671616 0.809 0.728 1.85E−48 Mt1 8.42E−53 0.890943921 0.701 0.556 2.09E−48 Gadd45g 9.92E−53 −0.340515267 0.503 0.639 2.46E−48 Apob 1.44E−52 0.267840983 0.989 0.989 3.59E−48 Hdlbp 3.91E−52 0.27404334 0.828 0.713 9.72E−48 Gjb2 6.01E−52 0.28026592 0.725 0.572 1.49E−47 Ndufa4 7.60E−52 −0.261719376 0.851 0.889 1.89E−47 Cml1 7.90E−52 −0.295319392 0.709 0.757 1.96E−47 Sfxn1 5.35E−51 0.262434679 0.636 0.496 1.33E−46 Thrsp 3.45E−50 −0.460250446 0.583 0.627 8.56E−46 Ssr3 6.72E−49 0.252936524 0.732 0.596 1.67E−44 mt-Atp6 2.06E−48 −0.419380785 0.311 0.452 5.11E−44 Rpl32 1.00E−47 −0.30384302 0.688 0.757 2.49E−43 Btg2 4.30E−45 0.263524699 0.401 0.241 1.07E−40 Hspe1 2.75E−44 −0.308522832 0.462 0.557 6.83E−40 Insig1 1.88E−43 0.254088613 0.597 0.426 4.67E−39 Mt2 7.29E−43 0.669743697 0.518 0.365 1.81E−38 Hsd3b3 2.62E−41 −0.282851137 0.519 0.605 6.51E−37 Serpina12 6.83E−41 −0.279022117 0.362 0.492 1.70E−36 S100a9 7.01E−39 0.317582792 0.058 0.004 1.74E−34 Prdx4 1.19E−38 −0.290503348 0.55 0.607 2.95E−34 Mup2 3.60E−37 −0.446904247 0.285 0.392 8.95E−33 Hbb-bt 1.55E−36 0.448173614 0.052 0.002 3.86E−32 Cox7a2 2.72E−36 −0.251096024 0.722 0.784 6.76E−32 Cyp2b10 2.41E−35 −0.502782767 0.493 0.542 5.98E−31 Ndufs6 3.36E−32 −0.272052906 0.678 0.724 8.33E−28 Krt18 5.62E−32 0.330676662 0.72 0.617 1.39E−27 mmu-mir-6240 1.64E−30 0.339455801 0.22 0.115 4.06E−26 Ndufb4 1.61E−29 −0.253090085 0.409 0.49 3.99E−25 Fos 3.19E−28 0.263299308 0.609 0.51 7.91E−24 Plin2 3.89E−27 0.371436511 0.799 0.714 9.66E−23 Rpl36al 8.10E−27 −0.2702077 0.495 0.551 2.01E−22 Mup1 1.57E−24 −0.470008649 0.522 0.583 3.91E−20 Rps15 4.98E−19 −0.272193403 0.49 0.528 1.24E−14 Ubb 5.31E−19 −0.264147083 0.394 0.45 1.32E−14 Etnppl 2.49E−17 0.263747104 0.647 0.606 6.18E−13 Gm26917 2.71E−16 0.39502224 0.253 0.181 6.74E−12 Ftl1 2.27E−15 −0.309991928 0.367 0.409 5.64E−11 Chka 1.77E−12 0.28917469 0.312 0.231 4.40E−08 mmu-mir-6236 0.004690575 0.257694673 0.868 0.837 1 Saa2 0.008288556 0.375915223 0.231 0.222 1

TABLE 14b PH vs UT Markers ID p_val avg_logFC pct.1 pct.2 p_val_adj Saa2 0 3.689742641 0.981 0.222 0 Saa1 0 2.953116544 0.999 0.662 0 Mt1 0 2.20137648 0.968 0.556 0 Mt2 0 2.140389237 0.934 0.365 0 Lcn2 0 1.982609697 0.862 0.07 0 Orm2 0 1.521515479 0.596 0.09 0 Serpina3n 0 1.468184429 0.935 0.574 0 Steap4 0 1.432404924 0.767 0.222 0 Gm26924 0 1.269761148 1 1 0 Apcs 0 1.231432603 0.878 0.525 0 n-R5-8s1 0 1.205558807 0.652 0.031 0 Fgl1 0 1.13936575 0.973 0.784 0 Hp 0 1.122408731 1 0.999 0 Orm1 0 1.121622286 0.996 0.952 0 Lars2 0 1.06369286 0.999 0.994 0 Itih4 0 1.059091356 0.997 0.948 0 Lrg1 0 1.054853379 0.964 0.736 0 Gm15564 0 1.050908678 0.991 0.956 0 Fga 0 0.99801394 0.998 0.997 0 Hpx 0 0.940144751 1 0.997 0 Itih3 0 0.937820769 0.983 0.89 0 Saa4 0 0.924382378 0.941 0.749 0 Igfbp1 0 0.91788643 0.881 0.717 0 mmu-mir-6236 0 0.830874915 0.969 0.837 0 C3 0 0.82839829 0.999 0.99 0 Gm23935 0 0.802263862 0.993 0.925 0 Gm24601 0 0.792992967 0.498 0.015 0 Serpina10 0 0.76903021 0.885 0.641 0 Fn1 0 0.767461447 0.941 0.821 0 Il1r1 0 0.756862098 0.606 0.167 0 Nnmt 0 0.755485266 0.906 0.716 0 Fgg 0 0.746061837 0.999 0.991 0 Tat 0 0.684122974 0.975 0.903 0 Fgb 0 0.682932942 1 1 0 Cfh 0 0.573278509 0.973 0.897 0 Mat1a 0 0.537803765 0.985 0.966 0 Pzp 0 0.475711355 0.993 0.986 0 Ambp 0 0.375515564 0.998 0.993 0 Kng1 0 0.374458693 0.995 0.991 0 Apoe 0 −0.300107411 1 1 0 Apoa2 0 −0.343336611 0.999 1 0 Acaa1b 0 −0.530837085 0.841 0.969 0 Ugt2b5 0 −0.569543251 0.934 0.959 0 Ces1d 0 −0.604928809 0.776 0.923 0 Gsta3 0 −0.626297488 0.952 0.956 0 Mup20 0 −0.646719137 0.983 1 0 mt-Rnr1 0 −0.656606417 1 1 0 Cyb5 0 −0.671123253 0.98 0.983 0 mt-Rnr2 0 −0.808086948 1 1 0 mt-Atp6 0 −0.874171981 0.096 0.452 0 Mup12 0 −0.892704406 0.548 0.86 0 Mup3 0 −0.904471306 1 1 0 Mup16 0 −0.969957455 0.672 0.934 0 Mup21 0 −1.050450968 0.552 0.929 0 Cyp2b10 0 −1.18690109 0.151 0.542 0 Gm13775 0 −1.201481557 0.193 0.761 0 mt-Nd2 0 −1.211183598 0.975 0.999 0 Mup15 0 −1.224451421 0.175 0.617 0 mt-Co3 0 −1.227561419 0.094 0.603 0 mt-Nd1 0 −1.258161993 0.985 1 0 Mup11 0 −1.280114586 0.964 1 0 mt-Nd5 0 −1.306454077 0.917 0.995 0 mt-Co2 0 −1.37598008 0.063 0.629 0 mt-Cytb 0 −1.393705562 0.967 0.999 0 mt-Co1 0 −1.443944016 0.959 0.999 0 Ankrd55 0 −1.559084018 0.273 0.696 0 Mup5 0 −1.635008876 0.359 0.839 0 mt-Nd4 0 −1.736336239 0.926 0.998 0 Mup4 0 −1.869924265 0.28 0.898 0 Mup17 0 −2.409962327 0.816 1 0 Mup9 0 −2.4152335 0.333 0.976 0 Mup6 0 −2.505776694 0.589 0.992 0 Mup18 0 −2.546220887 0.512 0.997 0 Mup19 0 −3.190512309 0.648 1 0 Rbp4 5.65E−307 −0.323113791 0.995 0.999 1.40E−302 Car3 1.27E−295 −0.584176786 0.908 0.974 3.16E−291 Lpin1 1.18E−294 0.866565964 0.66 0.31 2.93E−290 Mup13 3.27E−293 −0.819687605 0.201 0.546 8.12E−289 Clu 3.19E−291 0.456701196 0.986 0.958 7.92E−287 Fmo5 3.56E−281 0.516820181 0.936 0.837 8.84E−277 Scd1 5.92E−279 0.79323843 0.966 0.901 1.47E−274 Serpina3m 5.01E−275 0.584599049 0.873 0.722 1.24E−270 Tacc2 5.43E−271 0.548585735 0.428 0.071 1.35E−266 Slc39a14 1.76E−266 0.617728658 0.675 0.343 4.37E−262 Sephs2 1.85E−265 0.525890516 0.896 0.761 4.60E−261 Mup8 4.61E−265 −0.812904236 0.065 0.373 1.15E−260 Rnase4 1.95E−264 0.695293911 0.976 0.921 4.85E−260 Serpina3c 2.75E−263 −0.576033114 0.076 0.385 6.82E−259 Cxcl1 4.03E−262 0.809516105 0.645 0.314 1.00E−257 Qsox1 4.32E−257 0.54389261 0.887 0.707 1.07E−252 Egfr 1.70E−249 0.525141895 0.938 0.809 4.21E−245 Cp 3.84E−248 0.462891672 0.984 0.943 9.54E−244 Akr1c6 2.09E−247 −0.457244965 0.965 0.971 5.19E−243 Mup10 2.25E−246 0.340599862 0.899 0.692 5.58E−242 Cyp2c29 1.52E−245 −0.719965927 0.772 0.93 3.77E−241 Prg4 5.38E−245 0.577764422 0.549 0.188 1.34E−240 Cox4i1 4.28E−244 −0.421671698 0.933 0.958 1.06E−239 Cyp2c54 6.04E−243 −0.645057569 0.471 0.759 1.50E−238 Cyp3a11 2.52E−239 −0.296384714 0.999 1 6.25E−235 Plg 6.49E−234 0.359061279 0.987 0.961 1.61E−229 Ly6e 9.54E−234 0.714707911 0.683 0.386 2.37E−229 Hspb8 3.35E−233 0.531530338 0.812 0.597 8.32E−229 Mup2 7.36E−233 −0.693969951 0.098 0.392 1.83E−228 Sod1 7.22E−231 −0.322303248 0.983 0.983 1.79E−226 Vtn 9.66E−226 0.319614974 0.994 0.983 2.40E−221 Hnf4a 4.11E−221 0.49323747 0.875 0.743 1.02E−216 Fabp1 1.66E−220 −0.337243781 0.997 1 4.11E−216 Igfbp2 2.43E−220 −0.509220055 0.742 0.885 6.03E−216 Elovl3 1.67E−219 −0.552813954 0.619 0.827 4.14E−215 Pck1 2.26E−213 0.356838712 0.982 0.987 5.60E−209 Apoc4 4.63E−211 −0.333934616 0.985 0.98 1.15E−206 Mgst1 9.64E−211 −0.329076093 0.999 0.997 2.39E−206 Cyp2c50 1.98E−209 −0.605557967 0.707 0.888 4.92E−205 Cyp2c37 2.30E−201 −0.645818031 0.292 0.608 5.72E−197 Gjb2 3.64E−200 0.499499448 0.789 0.572 9.05E−196 Tifa 2.20E−197 0.319491862 0.306 0.036 5.46E−193 Btg2 7.63E−194 0.556244998 0.546 0.241 1.89E−189 Fkbp5 9.37E−192 0.393979234 0.427 0.117 2.33E−187 Ugt2b36 1.11E−191 −0.379582842 0.908 0.93 2.77E−187 C4bp 4.37E−189 0.413371192 0.921 0.788 1.09E−184 Cyp3a25 9.86E−189 −0.396588983 0.861 0.919 2.45E−184 Acox1 8.58E−186 0.351743194 0.97 0.966 2.13E−181 Actb 2.50E−182 0.376789439 0.956 0.886 6.22E−178 Cox6c 2.51E−182 −0.497413871 0.794 0.884 6.22E−178 Ahcy 1.37E−181 −0.430442246 0.835 0.916 3.40E−177 Slc38a2 2.21E−180 0.526051309 0.671 0.413 5.50E−176 mt-Nd6 1.13E−174 −0.578855337 0.303 0.577 2.81E−170 Igfbp4 2.03E−174 0.3361593 0.932 0.866 5.03E−170 Apob 1.78E−173 0.382325227 0.989 0.989 4.41E−169 Slc41a2 2.85E−173 0.382165778 0.423 0.134 7.07E−169 B3galt1 1.82E−172 0.521682374 0.446 0.163 4.53E−168 Glud1 3.14E−171 0.334724449 0.964 0.905 7.80E−167 P4hb 9.55E−171 0.304018972 0.983 0.941 2.37E−166 Slc25a25 4.57E−169 0.429973659 0.849 0.704 1.14E−164 Gm4076 2.11E−168 −0.343049018 0.006 0.184 5.25E−164 Cyp8b1 3.50E−167 −0.481824636 0.553 0.745 8.69E−163 Myh9 6.99E−167 0.49004916 0.601 0.318 1.74E−162 Hsd3b5 1.80E−161 −0.619275352 0.374 0.587 4.48E−157 Sdc4 6.03E−161 0.338637436 0.938 0.867 1.50E−156 Stat3 8.58E−161 0.435626527 0.596 0.318 2.13E−156 Uqcrq 1.69E−160 −0.375118557 0.933 0.951 4.20E−156 Lrp1 2.72E−160 0.552561179 0.792 0.591 6.77E−156 Cyp2a5 1.64E−158 −0.806866679 0.292 0.555 4.07E−154 Rps27l 2.91E−157 −0.450411941 0.748 0.849 7.24E−153 Faml34b 1.52E−155 0.505513689 0.637 0.405 3.76E−151 Snx10 1.02E−154 0.374844995 0.464 0.188 2.53E−150 Tmem176a 1.64E−154 0.468074534 0.671 0.429 4.06E−150 Arhgef26 6.46E−154 0.379910814 0.483 0.203 1.60E−149 Aldh1l1 7.31E−154 0.344751078 0.962 0.904 1.81E−149 Rsp14 1.24E−153 −0.359378616 0.859 0.917 3.09E−149 Slc10a2 1.69E−153 0.252457327 0.285 0.05 4.20E−149 Angptl3 2.80E−152 −0.315450205 0.944 0.944 6.95E−148 2810007J24Rik 5.24E−152 −0.351230039 0.876 0.943 1.30E−147 Dhcr24 4.52E−144 0.459081587 0.912 0.783 1.12E−139 Inmt 2.84E−143 −0.462286253 0.842 0.884 7.06E−139 Tmem176b 9.96E−143 0.449221175 0.803 0.632 2.47E−138 Ifitm3 5.65E−142 0.361933739 0.91 0.812 1.40E−137 Hc 1.34E−141 0.372595616 0.949 0.903 3.33E−137 Aass 2.32E−141 0.442569419 0.837 0.716 5.75E−137 Ctsb 3.68E−141 0.380577928 0.9 0.781 9.13E−137 Cpb2 6.91E−141 0.349207497 0.927 0.813 1.72E−136 Hyou1 8.18E−141 0.42831956 0.638 0.385 2.03E−136 Bcl3 1.44E−140 0.254384767 0.308 0.074 3.56E−136 Rcan1 9.55E−137 0.297888563 0.317 0.085 2.37E−132 St3gal5 1.41E−135 0.486994688 0.701 0.49 3.51E−131 Pfkfb3 3.04E−135 0.259894095 0.243 0.039 7.56E−131 Hrsp12 2.39E−134 −0.35371508 0.889 0.939 5.93E−130 Cox7b 2.39E−133 −0.426009228 0.809 0.878 5.93E−129 Sparcl1 2.50E−133 −0.253616986 0 0.136 6.22E−129 Cldn14 3.85E−132 0.28211242 0.298 0.076 9.56E−128 Errfi1 4.39E−131 0.31039351 0.953 0.911 1.09E−126 Apoa4 1.99E−129 0.679443346 0.572 0.339 4.93E−125 Rhob 5.41E−128 0.25813998 0.287 0.069 1.34E−123 Creg1 8.19E−128 −0.315552444 0.894 0.926 2.03E−123 Slc7a2 2.08E−124 0.399579476 0.823 0.735 5.17E−120 C4b 2.43E−124 0.391765742 0.937 0.883 6.04E−120 Itih2 3.35E−124 0.299717266 0.946 0.884 8.32E−120 Abca1 4.28E−124 0.403462344 0.621 0.377 1.06E−119 Hsp90ab1 1.07E−123 0.279914616 0.967 0.922 2.66E−119 Lbp 6.64E−123 0.38653516 0.577 0.333 1.65E−118 Calr 2.26E−122 0.28388138 0.937 0.885 5.61E−118 Pon1 2.91E−120 −0.337990401 0.868 0.906 7.23E−116 Etnk2 1.29E−119 0.372806041 0.793 0.655 3.21E−115 Mtss1 1.02E−118 0.372989855 0.657 0.454 2.54E−114 Ndufb6 8.09E−118 −0.413332747 0.651 0.759 2.01E−113 Gm20594 1.01E−117 −0.541666642 0.102 0.294 2.50E−113 Serping1 1.10E−117 0.304093562 0.933 0.87 2.74E−113 Slc25a15 4.49E−117 0.330021491 0.856 0.738 1.12E−112 Lpgat1 1.65E−116 0.384155769 0.7 0.502 4.10E−112 Grn 2.86E−115 0.350498754 0.627 0.396 7.10E−111 Plin2 5.72E−115 0.400511805 0.807 0.714 1.42E−110 H3f3b 8.65E−115 0.440105486 0.62 0.419 2.15E−110 Ech1 2.35E−113 −0.335883409 0.78 0.856 5.83E−109 Gm26917 2.94E−113 0.46154986 0.413 0.181 7.31E−109 Zfp683 5.62E−113 −0.421689112 0 0.116 1.40E−108 Rbp1 2.51E−111 0.25848775 0.266 0.069 6.24E−107 Rnf125 4.39E−111 −0.401552322 0.295 0.493 1.09E−106 Bhlhe40 5.21E−111 0.31908752 0.493 0.251 1.29E−106 Mfsd2a 1.96E−110 0.296148518 0.376 0.148 4.86E−106 Ndufb11 6.07E−110 −0.41040464 0.611 0.735 1.51E−105 Cyp2d9 4.91E−108 −0.27539583 0.94 0.959 1.22E−103 Rps2 1.52E−107 −0.4101328 0.613 0.757 3.78E−103 Comt 1.91E−107 0.259910468 0.965 0.931 4.74E−103 Atf3 2.53E−107 0.402014064 0.399 0.179 6.29E−103 Bach1 1.21E−106 0.286794151 0.372 0.151 2.99E−102 Aadac 1.56E−106 −0.407054513 0.84 0.86 3.87E−102 C8a 2.53E−106 0.300098611 0.933 0.887 6.29E−102 Cps1 5.25E−106 0.254838343 0.978 0.971 1.30E−101 Gfra1 9.01E−106 0.342777741 0.696 0.498 2.24E−101 Eef1a1 1.02E−105 0.27081899 0.913 0.85 2.53E−101 Chchd2 3.57E−105 −0.334788452 0.875 0.916 8.85E−101 Plk3 1.17E−104 0.3008626 0.458 0.226 2.90E−100 Cfi 1.89E−104 0.259039083 0.953 0.905 4.69E−100 Shb 1.40E−103 0.277770125 0.432 0.204 3.47E−99  Mpeg1 3.00E−103 0.287855502 0.286 0.089 7.45E−99  Cfhr2 1.38E−102 −0.383650774 0.851 0.868 3.43E−98  H6pd 7.14E−102 0.329467549 0.747 0.595 1.77E−97  Retsat 3.66E−101 −0.353340297 0.69 0.83 9.09E−97  Atp5f1 4.54E−101 −0.336466912 0.845 0.869 1.13E−96  Acsl1 5.82E−101 −0.318662804 0.854 0.924 1.44E−96  Itih1 5.89E−101 0.301421351 0.906 0.816 1.46E−96  Ugt2b34 1.10E−100 −0.304452716 0.834 0.874 2.72E−96  Malat1 1.50E−100 −0.401852303 0.613 0.78 3.72E−96  Tgm2 7.01E−100 0.337876607 0.477 0.258 1.74E−95  Ndufa4 1.87E−99  −0.338157892 0.843 0.889 4.63E−95  Saa3 2.83E−98  1.098349208 0.272 0.087 7.03E−94  Dap 5.60E−98  0.318746478 0.802 0.654 1.39E−93  Cyp2c70 7.42E−98  0.309156286 0.927 0.834 1.84E−93  Cdkn1a 1.98E−97  0.305119488 0.418 0.195 4.92E−93  Egr1 8.67E−97  0.418876559 0.627 0.447 2.15E−92  Slc3a1 1.14E−96  0.32839591 0.401 0.189 2.84E−92  Tnfrsf1a 3.20E−96  0.294748954 0.466 0.244 7.96E−92  Alas1 2.50E−95  0.322730245 0.857 0.729 6.20E−91  Hsd3b7 2.77E−95  −0.344848377 0.732 0.798 6.88E−91  Litaf 1.88E−93  0.304879493 0.49 0.278 4.67E−89  Ifitm2 5.90E−93  0.309819544 0.55 0.347 1.46E−88  Xbp1 6.66E−93  0.326303947 0.727 0.57 1.65E−88  Esd 7.38E−93  −0.332305281 0.701 0.784 1.83E−88  Eif4g2 1.69E−92  0.318021838 0.812 0.678 4.20E−88  Cyp4a10 4.95E−92  −0.425069794 0.481 0.657 1.23E−87  Gpt2 2.14E−91  0.303778712 0.817 0.725 5.32E−87  Cml2 5.10E−91  0.279615284 0.921 0.857 1.27E−86  Cth 1.52E−90  −0.324114713 0.818 0.838 3.77E−86  Trib1 1.01E−89  0.345110824 0.51 0.308 2.52E−85  Ephx2 1.32E−89  −0.279612105 0.886 0.937 3.27E−85  Mpc2 4.49E−89  −0.292946135 0.806 0.857 1.11E−84  Sult1a1 4.64E−89  0.326135758 0.813 0.707 1.15E−84  Rpl13a 5.96E−89  −0.255832076 0.8 0.868 1.48E−84  Got1 1.28E−88  0.349895796 0.73 0.587 3.18E−84  Gm10250 8.85E−88  −0.316106405 0.095 0.251 2.20E−83  Slc25a22 1.55E−86  0.257081972 0.495 0.282 3.84E−82  Glul 1.80E−86  0.516246513 0.385 0.18 4.47E−82  Rapgef4 2.38E−85  0.320885046 0.62 0.436 5.90E−81  Adck3 5.88E−84  −0.332543616 0.695 0.764 1.46E−79  Ang 9.86E−84  0.394462539 0.811 0.687 2.45E−79  Xdh 1.19E−83  0.28935916 0.472 0.258 2.95E−79  Man2a1 1.36E−83  0.31713355 0.734 0.583 3.38E−79  Epas1 1.79E−83  0.265618306 0.505 0.297 4.44E−79  Selenbp2 4.88E−83  −0.258842945 0.867 0.937 1.21E−78  Txnip 5.00E−83  0.280540465 0.51 0.297 1.24E−78  Cd51 9.74E−82  0.30004343 0.158 0.026 2.42E−77  Fabp2 3.34E−81  −0.375664441 0.473 0.622 8.30E−77  Fh1 4.65E−81  0.2953128 0.798 0.648 1.16E−76  Ugt2a3 1.16E−80  −0.326140058 0.686 0.773 2.88E−76  Gm5096 3.98E−80  −0.368621118 0.314 0.468 9.88E−76  Oaz1 4.28E−80  −0.35427991 0.673 0.75 1.06E−75  Hsd11b1 1.51E−79  −0.28823804 0.819 0.875 3.74E−75  Hrg 5.55E−79  0.287679276 0.911 0.831 1.38E−74  Atp5j 1.74E−78  −0.306893156 0.658 0.757 4.31E−74  Gstm1 2.88E−78  −0.312458518 0.91 0.935 7.16E−74  Uroc1 9.57E−78  0.326783149 0.741 0.615 2.38E−73  Ivns1abp 9.91E−78  0.281892175 0.512 0.315 2.46E−73  Hdlbp 1.25E−77  0.295510036 0.823 0.713 3.11E−73  Mvd 1.52E−77  −0.257890778 0.112 0.269 3.78E−73  Clec4f 1.69E−77  0.286061284 0.184 0.043 4.20E−73  Gpcpd1 1.51E−76  0.282654586 0.587 0.398 3.74E−72  Ndufa6 2.82E−75  −0.322691385 0.745 0.798 7.00E−71  Atp5h 1.24E−73  −0.414641214 0.575 0.682 3.08E−69  Ndufb9 3.72E−73  −0.256394271 0.841 0.888 9.23E−69  Il6st 9.58E−73  0.286771056 0.472 0.273 2.38E−68  Ces1f 1.88E−72  −0.281138036 0.759 0.817 4.68E−68  Clpx 4.35E−72  −0.31005374 0.733 0.783 1.08E−67  Fam35a 6.84E−72  0.255039805 0.435 0.246 1.70E−67  Kmo 2.31E−70  0.256834292 0.822 0.732 5.74E−66  Fos 2.62E−70  0.342537163 0.66 0.51 6.52E−66  Hagh 2.65E−70  −0.26145888 0.835 0.858 6.58E−66  Atp5j2 7.98E−70  −0.286422324 0.796 0.852 1.98E−65  Hebp1 1.62E−69  −0.296503386 0.67 0.75 4.03E−65  Ces2a 1.70E−69  −0.282358828 0.765 0.846 4.21E−65  Gm9843 1.88E−69  −0.34994897 0.155 0.299 4.66E−65  Cyb5r3 2.44E−69  0.263785288 0.824 0.725 6.06E−65  Hint2 3.13E−69  −0.327239077 0.589 0.676 7.76E−65  Mup7 5.98E−69  −0.564270613 0.974 0.998 1.48E−64  Cpt1a 3.17E−66  0.268110758 0.758 0.651 7.88E−62  Cyp3a13 9.97E−65  0.262155243 0.717 0.569 2.48E−60  Mup1 2.02E−64  −0.63630453 0.454 0.583 5.02E−60  Upp2 3.37E−64  0.284431808 0.761 0.673 8.36E−60  Aqp8 4.21E−64  −0.318028572 0.372 0.505 1.05E−59  Uqcr11 5.01E−64  −0.256632134 0.833 0.879 1.24E−59  Fasn 1.22E−62  0.272244147 0.527 0.345 3.03E−58  Wbp1l 2.18E−62  0.251700028 0.732 0.606 5.40E−58  Mtusl 5.66E−62  0.30024906 0.596 0.42 1.40E−57  Jun 5.97E−62  0.293637263 0.723 0.593 1.48E−57  Uqcrh 9.05E−62  −0.279749266 0.742 0.81 2.25E−57  Ddx3x 1.29E−61  0.264853975 0.655 0.513 3.21E−57  Ell2 5.00E−61  0.250568745 0.582 0.416 1.24E−56  Hsph1 5.93E−61  0.270501218 0.434 0.255 1.47E−56  Krt18 1.41E−60  0.282094099 0.735 0.617 3.50E−56  Atp2a2 1.67E−58  0.260679425 0.645 0.495 4.15E−54  Fam25c 6.81E−55  0.371649508 0.519 0.356 1.69E−50  Cox5b 5.78E−52  −0.290064648 0.621 0.726 1.43E−47  Ppp2r5a 5.65E−49  −0.281184325 0.506 0.594 1.40E−44  Glo1 2.28E−48  −0.255075136 0.682 0.749 5.65E−44  Mug2 1.71E−47  0.260256341 0.813 0.738 4.24E−43  1110008F13Rik 1.62E−46  −0.258608944 0.559 0.648 4.03E−42  Cyp1a2 1.66E−46  −0.252439299 0.704 0.794 4.11E−42  Prdx4 2.77E−43  −0.286424739 0.534 0.607 6.87E−39  Rpl14 2.85E−43  −0.261131992 0.474 0.574 7.07E−39  Cox7a2 6.39E−41  −0.253037939 0.746 0.784 1.59E−36  Sco2 4.21E−39  −0.257919482 0.407 0.508 1.04E−34  Rabac1 6.06E−39  −0.261231844 0.428 0.524 1.51E−34  Ndufc2 2.62E−38  −0.293093496 0.518 0.579 6.51E−34  Mup14 3.52E−38  −0.4939069 0.539 0.616 8.73E−34  Slc25a47 5.57E−37  0.255728584 0.908 0.927 1.38E−32  Uqcrb 1.37E−33  −0.261145805 0.583 0.641 3.41E−29  Nr1i3 2.64E−32  −0.254276065 0.277 0.377 6.54E−28  Thrsp 8.05E−31  0.301660902 0.712 0.627 2.00E−26  Ftl1 1.01E−21  −0.326164787 0.35 0.409 2.50E−17  Sds 3.64E−15  0.384727442 0.641 0.67 9.04E−11 

To validate these findings in a spatiotemporal context, Applicants queried the distribution of the pericentral markers Cyp2e1 and Glu1 using smFISH analyses (FIG. 19A, 19E; FIG. 27A-27D). Cyp2e1 extended further into the lobular midzone following APAP exposure, with pericentral necrosis at A6 and A24 (FIG. 19B). Expression then normalized at A48, following the cell proliferative response. Glu1 expression is normally restricted to a single layer of cells surrounding the central vein²⁵, which underwent necrosis following APAP overdose (FIG. 19B). Surprisingly, Glu1 was now expressed at low levels across the entire liver lobule indicating an effort to maintain Glu1 expression, but (A6, A24, FIG. 19B). Glu1 expression patterns returns to normal by A48 (FIG. 19B). These findings reveal compensatory expression of pericentral genes through adaptive reprogramming of midzonal hepatocytes after pericentral toxic injury.

In contrast to APAP, PH does not produce zone-dependent injury but a massive loss of ˜70% of liver cell mass (compared to ˜10% total cell loss after APAP exposure), imposing extreme functional demand on the remaining hepatocytes. Functional compensation was also observed after PH, evident from a dramatic increase in Glu1+ hepatoctyes (FIG. 18G) from 18% (Control) to 60% (P3). This is further supported by the observation that Cyp2e1+ hepatocytes only decrease by 18% (67% to 49%) at P3 (FIG. 18G). smFISH analysis confirmed increased expression zones and total expression levels for both Cyp2e1 and Glu1 in PH (FIG. 19C). In addition, Applicants observed functional compensatory up-regulation of the periportal marker Arg1 suggesting that adaptive reprogramming of hepatocytes is not exclusive to pericentral genes (FIG. 27D). These results highlight that zonal transcriptional compensation is independent of the form of liver injury occurring after both zone-specific injury and also after massive cellular loss.

Acute Liver Injury Causes Both Injury-Specific and Non-Specific Responses

To further define shared and unique responses in both liver injury models, Applicants determined differentially expressed genes (DEG) between each treatment condition and untreated controls (UT), and then pooled results to reveal composite DEG results for APAP and PH (Methods, Table 8a, 8b), for which Applicants performed select validations using smFISH (FIG. 20 , FIG. 28A-28D). A number of gene expression alterations could be attributed to injury-dependent effects. A large number of gene expression changes, however, were shared between the two models, indicating they do not reflect the specific nature of injury (FIG. 20A, 20B, Table 15a-b). Gene set analysis (GSA) revealed an enrichment of pathways involved in toxic injury within the APAP model, including GO Acute Inflammatory Response, Hallmark Xenobiotic Metabolism, Go Acute Phase Response, Go Regulation of Fatty Acid Metabolic Process, Go Organic Hydroxy Compound Metabolic Process, KEGG PPAR Signaling Pathway, Go Regulation of Extrinsic Apoptotic Signaling Pathway, Go Organic Acid Metabolic Process, Hallmark Bile Acid metabolism, Go Regulation of Steroid Metabolic Process. (FIG. 20C, Tables 16A-16C of U.S. Provisional Application 62/925,693, filed Oct. 24, 2019, and incorporated herein by reference)²⁶. The PH model, meanwhile, exhibited an enrichment among pathways involved in cell proliferation, which could be attributed to differences in the extent of injury between the two models (FIG. 20C, Tables 16A-16C of U.S. Provisional Application 62/925,693, filed Oct. 24, 2019, and incorporated herein by reference). Pathway enrichments unique to PH may include Vesicle Mediated Transport, Phospholipid Binding, Enzyme Linked Receptor Protein Signaling Pathway, Response to Growth Factor, Response to Abiotic Stimulus, Wong Adult Tissue Stem Module, Cellular Response to Stress, Regulation of Growth, Regulation of Cell Proliferation. Following APAP overdose, there was a substantial anti-oxidant response by GSA and expression of individual anti-oxidant response genes, such as thioredoxin (Txnrd1) and glutamate-cysteine ligase subunit c (Gclc) (FIG. 20D). Pathway Enrichments shared between APAP and PH may include Glycerolipid Metabolic Process, Extracellular Matrix, Platelet Degranulation, Exocytosis, Wound Healing, Negative Regulation of Peptidase Activity, Response to Biotic Stimulus, Regulation of Hydrolase Activity, Ion Homeostatis, and Enzyme Regulator Activity, associated with liver functions healing. (FIG. 13, 20C) Surprisingly, smFISH analysis revealed an up-regulation of Txnrd1 and Gclc across the entire liver lobule reaching into the periportal region (FIG. 20D). These findings suggest that some injury responses are not exclusive to the region of injury.

TABLE 15a Shared composite DEG. Table of genes with concordant (up or down) regulation relative to untreated in both APAP and PH. NA indicates that a particular gene was not significantly differentially expressed. avg_logFC_APAP avg_logFC_PH p_val_adj_APAP p_val_adj_PH A6logFC A24logFC Mup11 −3.2139532 −1.76921 0 0 −3.2139532 −1.6114348 Mup19 −2.3963453 −3.63217 0 0 −2.39634529 −1.6993527 Mup17 −2.3543586 −2.51447 0 0 −2.35435856 −1.8003486 Fabp1 −1.0161748 −0.82649  1.10E−198 0 −1.01617485 NA Akr1c6 −1.58626 −0.50114  2.54E−187  6.85E−150 −1.58626 −0.3176388 Mgst1 −1.0601549 −0.36875  2.13E−181  2.50E−131 −1.06015485 NA Mup9 −2.004164 −2.52066 0 0 −2.004164 −1.8474469 Apoc1 −0.8712827 −0.31074  7.90E−242 1.04E−90 −0.87128274 −0.3803368 Mup16 −1.6020855 −1.24514 0 0 −1.60208554 −1.0189759 Adh1 −1.2550282 −0.29598  1.90E−167  3.27E−106 −1.25502821 −0.342019  Cyp2e1 −2.3185702 −0.3015  4.79E−166 4.23E−36 −2.31857016 −0.4990336 Gpx1 −0.7685563 −0.32198  6.77E−238  2.36E−120 −0.76855633 −0.5079714 Mup3 −0.8062194 −1.42376 0 0 −0.70348317 −0.8062194 Mup18 −1.7271783 −2.61774 0 0 −1.62795678 −1.7271783 Apoc4 −1.0022658 −0.50176  9.54E−150  1.19E−182 −1.00226577 −0.4284969 Mup6 −2.0320849 −2.64537 0 0 −1.87185204 −1.6781848 Nudt7 −1.5642669 −0.56604  2.67E−255 9.48E−52 −1.56426694 NA Mup12 −1.2699737 −1.22808  1.14E−185 0 −1.26997373 NA Car3 −1.0360931 −1.29219  1.61E−124 0 −1.03609313 NA Apoa2 −0.5455185 −0.61598 0 0 −0.54278496 −0.5455185 Selenbp2 −1.190222 −0.8572 0  9.70E−194 −1.00916572 −0.3833246 2810007J24Rik −0.9143011 −1.094  6.76E−113  2.63E−273 −0.91430112 NA Uqcrq −0.8866551 −0.48535  1.50E−140  2.42E−124 −0.88665513 −0.595921  Ttr −0.5306256 −0.28614  5.79E−264 3.87E−82 −0.53062564 NA Cyp2c29 −1.14963 −1.02727 1.97E−99  2.76E−235 −1.14962998 −0.5860034 Tmem205 −0.7747427 −0.36376 1.05E−96 6.01E−57 −0.77474273 −0.4721077 Gsta3 −0.8062905 −0.79693  2.44E−166  3.08E−250 −0.80629047 −0.6693549 Cyb5 −0.7101896 −0.75169  8.36E−212 0 −0.71018958 −0.7048085 Hsd3b7 −1.0059958 −0.58164 3.79E−93 5.15E−93 −1.0059958 −0.3952566 Acaa1b −0.8508413 −0.85553  4.51E−247 0 −0.73282346 −0.8508413 Gm13775 −1.0780882 −1.25566  1.37E−292 0 −1.06561886 −1.0324519 Psen2 −0.9473738 −0.41956 1.77E−85 1.69E−77 −0.94737377 NA Mup15 −1.3164641 −1.36418  1.22E−233  5.96E−268 −1.31646415 −1.2349284 Cyp8b1 −0.8892298 −0.59929 8.76E−88  1.54E−120 −0.88922983 −0.5536162 Rps27l −0.8659275 −0.64582 5.43E−90  1.42E−139 −0.86592748 −0.5485062 Cox6c −0.8442805 −0.61022 3.24E−81  2.30E−132 −0.84428054 −0.5028028 Ugt2b5 −0.6033512 −0.71634  9.60E−175  5.77E−289 −0.60335125 −0.5764988 Hsd3b5 −1.0695202 −0.88646  1.41E−154  3.58E−129 −1.06952022 NA Cyp2a5 −1.4989102 −0.93818 3.74E−79  8.06E−111 −1.49891017 −0.681078  Ugt2b1 −0.7768169 −0.7221 2.28E−76  5.69E−140 −0.77681693 −0.2894617 Cyp1a2 −0.9939358 −0.48192 1.08E−75 3.86E−66 −0.99393584 NA Hgd −0.7585723 −0.274 1.96E−75 2.46E−30 −0.75857227 NA Adck3 −0.8761154 −0.56969 2.27E−75 4.38E−91 −0.87611538 −0.2825153 Mup21 −1.0081719 −1.63781 0 0 −0.82724993 −0.6977358 Cyp2d9 −0.6406986 −0.61668  3.96E−157  8.72E−151 −0.64069861 −0.5671662 Apoe −0.4212717 −0.61588 0 0 −0.36896653 −0.4212717 mt-Nd4 −1.9574248 −1.95321 0 0 −0.63884813 −1.9574248 C8g −0.6545103 −0.45564 4.13E−96 2.41E−80 −0.65451026 −0.4819645 Mup7 −1.1155878 −0.84773 0  8.04E−142 −0.94137049 NA Ubc −0.6618397 −0.27324 4.04E−67 3.58E−41 −0.66183972 −0.3704876 Pon1 −0.6857513 −0.42826 1.66E−66 1.97E−64 −0.68575128 −0.3227485 Oaf −0.7328674 −0.33377  1.03E−122 3.11E−47 −0.7328674 NA Ugt2b36 −0.5834315 −0.62967 1.36E−63  1.10E−145 −0.58343149 −0.3293162 Ces3a −0.5253364 −0.72101 5.80E−77  1.41E−206 −0.52533635 −0.3687356 Mup5 −1.3706213 −1.77461  1.94E−240 0 −1.23728834 −1.3706213 Ndufa4 −0.6831267 −0.51272 3.70E−65  4.13E−107 −0.6831267 −0.4433111 Hagh −0.6740097 −0.39811 1.62E−61 4.45E−73 −0.67400971 NA Cyp3a11 −0.4231307 −0.80355  1.05E−122 0 −0.42313075 −0.3638912 Hsd3b3 −0.7795011 −0.34746 1.98E−61 3.82E−42 −0.77950112 NA Hint1 −0.6738806 −0.48702 1.71E−80  9.22E−101 −0.67388058 −0.4736653 Scp2 −0.5191249 −0.31952  3.33E−100  5.16E−159 −0.51912492 NA Cox4i1 −0.5159892 −0.57523  4.62E−112  2.23E−168 −0.51598917 −0.4542436 Sod1 −0.4393198 −0.48337 3.30E−72  3.17E−216 −0.4393198 −0.3036291 Hacl1 −0.7068977 −0.3329 1.20E−59 4.71E−52 −0.70689773 NA Hpd −0.5181804 −0.31794 2.47E−59 2.00E−54 −0.51818039 −0.313324  mt-Co2 −1.3965432 −1.41733  7.79E−219 0 −1.10533286 −1.3965432 Cyp2c37 −0.8869038 −0.82039 9.93E−57  2.10E−130 −0.88690378 −0.4875226 Inmt −0.7310164 −0.67979 1.21E−55  1.56E−139 −0.7310164 −0.4435295 Uox −0.5531155 −0.48042 6.13E−55 1.42E−89 −0.55311551 NA Uqcr11 −0.60308 −0.36807 1.37E−54 8.58E−61 −0.60307999 −0.2632414 Ankrd55 −1.8735659 −1.95094  4.38E−235  2.52E−247 −1.25083463 −1.8735659 Prdx1 −0.5292291 −0.35376 1.10E−92 2.27E−73 −0.52922911 −0.2676651 Hebp1 −0.6354323 −0.31301 1.18E−51 1.26E−40 −0.63543227 NA Cox7b −0.6422408 −0.65009 3.42E−51  3.36E−144 −0.64224078 −0.2673975 mt-Nd1 −1.4196836 −1.544 0 0 −0.38833608 −1.4196836 Cox7a2 −0.6503384 −0.4411 2.00E−48 3.27E−59 −0.65033839 −0.363458  Chchd2 −0.5525035 −0.51862 7.88E−56  1.10E−119 −0.55250349 −0.3949168 Rarres2 −0.5521946 −0.49201 3.29E−48 1.76E−89 −0.55219458 −0.2666165 Ndufa6 −0.61365 −0.41844 4.43E−48 3.80E−59 −0.61364998 −0.3068153 Rdh7 −0.418626 −0.49691  6.63E−181  5.58E−132 −0.41862596 −0.2690433 Pah −0.522077 −0.37985 1.25E−47 8.65E−60 −0.52207695 NA Leap2 −0.6713009 −0.40479 1.25E−47 1.27E−50 −0.67130094 −0.2747781 Cyp7b1 −0.6580227 −0.43816 3.09E−98 1.37E−54 −0.65802273 NA Cyp2c50 −0.6618233 −0.76391 2.92E−46  8.52E−186 −0.6618233 −0.2904835 Mup4 −1.0870385 −1.94565  9.25E−125 0 −0.99530818 −1.0870385 Cml1 −0.6142405 −0.47269 1.70E−43 5.55E−63 −0.61424052 −0.3269095 Aadac −0.619958 −0.74734 4.18E−43  6.76E−122 −0.61995803 −0.4037666 Mup13 −0.7757431 −0.87508 2.45E−76  6.29E−165 −0.77574306 −0.6948897 Ttc39c −0.6362749 −0.28961 2.03E−42 2.34E−27 −0.63627493 NA Aldh1a1 −0.4787974 −0.40245 1.02E−41  1.39E−102 −0.47879745 NA Ddt −0.5222211 −0.34584 1.33E−60 1.40E−46 −0.52222115 −0.4224109 Cox6a1 −0.4872287 −0.39062 1.78E−87 1.67E−61 −0.48722865 −0.3666972 Atp5j2 −0.5130805 −0.40958 3.32E−40 3.23E−66 −0.51308051 NA Ndufb2 −0.5771545 −0.33686 1.66E−45 1.21E−30 −0.57715446 −0.3412263 Ndufb9 −0.5038288 −0.4837 5.48E−40  1.07E−104 −0.50382881 NA Atp5h −0.6398091 −0.5555  1.41E−124 7.99E−68 −0.6398091 −0.5794989 Qdpr −0.5235738 −0.3166 1.45E−39 1.80E−33 −0.52357376 NA Atp5f1 −0.5170612 −0.46071 2.05E−39 1.10E−77 −0.51706117 −0.2872403 Serpina1a −0.675202 −0.35537  4.32E−247 6.23E−81 −0.37845707 −0.675202  Fabp2 −0.6155693 −0.52719 4.18E−38 2.63E−76 −0.61556934 −0.3921961 Khk −0.4914532 −0.53015 1.03E−67 8.89E−91 −0.49145322 −0.297617  Mpc2 −0.4828394 −0.39521 7.20E−37 2.71E−68 −0.48283942 NA Ndufb6 −0.5076826 −0.51838 4.30E−35 3.96E−85 −0.50768256 −0.3064033 Elovl3 −0.675967 −0.92485  6.30E−121  1.57E−229 −0.50672414 −0.675967  Arl4d −0.5072283 −0.32852 6.71E−35 5.36E−30 −0.50722832 NA Akr1c14 −0.5185708 −0.28017 1.08E−34 1.20E−21 −0.5185708 NA Csad −0.559786 −1.21486 1.92E−72  5.27E−267 −0.55978602 −0.5312525 Ndufb11 −0.5096711 −0.47904 8.28E−53 2.10E−70 −0.50967106 −0.4275253 Cox5b −0.4987836 −0.39369 4.68E−34 3.39E−45 −0.49878362 −0.337825  Rplp1 −0.504663 −0.27482 4.91E−34 6.89E−20 −0.50466296 −0.2866404 Fxyd1 −0.4799084 −0.27342 3.83E−34 2.95E−25 −0.4799084 −0.3117591 Atp5j −0.4837353 −0.41538 3.59E−33 7.16E−66 −0.48373528 NA Rpl32 −0.5322184 −0.49859 1.10E−32 4.42E−73 −0.53221838 −0.2549101 Dio1 −0.5452837 −0.46973 1.11E−32 9.15E−59 −0.54528374 NA Nit2 −0.4859406 −0.25532 4.49E−32 6.79E−25 −0.48594061 NA Gnmt −0.4603611 −0.28818  1.33E−133 8.65E−84 −0.33340449 −0.4603611 Ssr4 −0.5075772 −0.28316 1.87E−31 7.71E−23 −0.50757724 NA Ndufs6 −0.5379298 −0.34104 2.00E−31 2.06E−29 −0.53792983 −0.359161  Etfb −0.3654903 −0.27001 4.01E−31 4.81E−54 −0.36549028 NA Rsp14 −0.402093 −0.60751 1.07E−73  3.76E−152 −0.40209304 −0.292251  Blvrb −0.5451127 −0.35108 6.23E−30 2.20E−30 −0.54511272 NA Uqcr10 −0.4519019 −0.38232 2.60E−29 1.93E−47 −0.45190185 NA Cyp3a25 −0.3860949 −0.41646  1.19E−134  5.44E−129 −0.38609486 NA Mup8 −0.795757 −0.82996  1.23E−114  3.80E−123 −0.75257771 −0.6133344 Sc5d −0.5009009 −0.27429 3.57E−48 3.96E−19 −0.50090092  0.34501688 Adipor2 −0.4737915 −0.25255 3.14E−27 1.11E−22 −0.47379151 NA Rpl36a1 −0.4755414 −0.33184 1.26E−26 3.44E−26 −0.47554139 NA Serpina1e −0.6620459 −0.7252 0 0 −0.26841379 −0.2843446 Serpina1d −0.4940072 −0.58685  1.74E−184  5.86E−199 −0.28901122 −0.4940072 Dcxr −0.4408516 −0.27134 2.61E−43 1.59E−18 −0.44085162 −0.4106665 Cmbl −0.4427064 −0.26537 1.48E−28 9.66E−25 −0.44270644 −0.312422  Ndufb4 −0.453693 −0.33169 3.64E−28 2.14E−33 −0.45369304 −0.3251455 B2m −0.4179739 −0.43085  1.86E−102 2.11E−97 −0.33035492 −0.4179739 Cyp4a12a −0.4568275 −0.47604 6.69E−26 1.00E−65 −0.45682749 NA Hspe1 −0.4807349 −0.25791 9.37E−26 3.13E−12 −0.48073495 −0.290583  Uqcrh −0.4291645 −0.48311 1.41E−25 5.89E−83 −0.42916452 NA mt-Co3 −1.1670277 −1.23396  4.34E−176  1.47E−287 −0.70593061 −1.1670277 Minos1 −0.455548 −0.3084 2.00E−25 8.00E−23 −0.45554803 NA Mup14 −0.7607669 1 2.64E−96 8.52E−68 −0.69746981 NA Cfhr2 −0.4484632 −0.63062 2.09E−34 7.59E−98 −0.44846316 −0.3219287 Timm13 −0.4329618 −0.26627 2.46E−24 1.44E−18 −0.4329618 NA 1500017E21Rik −0.4609972 −0.51793 2.47E−24 1.93E−69 −0.46099722 NA Hint2 −0.4243211 −0.37377 6.90E−37 2.60E−44 −0.4243211 −0.3701685 Pbld1 −0.442543 −0.26463 4.53E−92 2.23E−23 −0.44254299 NA Glo1 −0.406574 −0.37923 1.87E−23 3.51E−47 −0.40657402 NA Rpl13a −0.3814621 −0.48017 3.58E−22 2.24E−99 −0.38146214 NA Ces3b −0.3663797 −0.81956 5.30E−27  6.86E−161 −0.36637965 −0.2866854 Rps18 −0.4885408 −0.41508 8.18E−22 1.19E−34 −0.4885408 NA Serpina12 −0.4533994 −0.61237 2.90E−24 7.52E−89 −0.45339936 NA Ndufa2 −0.3964736 −0.30831 2.46E−21 9.67E−23 −0.39647363 NA Mup1 1 −0.88291 7.40E−25 1.78E−91 −0.73772733 −0.2618377 Bphl −0.4074792 −0.29948 5.02E−21 1.70E−33 −0.40747923 NA Prdx4 −0.4175889 −0.37802 6.96E−24 3.39E−40 −0.41758889 −0.3074421 Cyp2c54 −0.3949376 −0.71286 9.37E−37  1.75E−163 −0.39493764 −0.3268597 Rps2 −0.3878627 −0.47452 5.09E−44 4.24E−69 −0.38786266 −0.3844542 Acsl1 −0.370317 −0.56803 1.12E−70  3.63E−104 −0.34342401 −0.370317  Cebpa −0.391553 −0.48161 3.89E−20 2.92E−66 −0.39155301 NA Uqcrb −0.4084167 −0.35966 6.59E−20 6.07E−33 −0.40841674 NA 1110008F13Rik −0.4552706 −0.32748 4.13E−58 1.42E−34 −0.37509166 −0.4552706 Tmem243 −0.3790533 −0.27511 2.35E−20 2.06E−22 −0.37905328 −0.2655515 Atp5g3 −0.3002218 −0.35725 4.43E−19 1.87E−78 −0.30022182 NA Rps15 −0.455155 −0.32454 7.79E−24 3.43E−16 −0.45515504 −0.3561377 Nme1 −0.4328853 −0.29161 5.43E−19 9.48E−21 −0.43288531 NA Timm8b −0.3935819 −0.25099 8.39E−19 2.42E−15 −0.3935819 NA Ndufc2 −0.4252848 −0.37134 1.02E−18 1.56E−33 −0.42528482 −0.3080394 S100a1 −0.3761862 −0.35554 1.76E−35 2.21E−35 −0.37433812 −0.3761862 Sdhd −0.3352613 −0.3023 8.20E−61 2.47E−32 −0.33526125 NA Usmg5 −0.4304948 −0.28365 4.55E−56 1.10E−10 −0.43049483 NA Cyp27a1 −0.3735103 −0.32623 4.44E−19 1.46E−36 −0.37351033 −0.2515784 Rps3 −0.3493208 −0.3399 5.25E−18 7.09E−57 −0.34932075 NA Slc22a30 −0.3745984 −0.33187 5.26E−18 7.77E−38 −0.3745984 NA Rps9 −0.3717938 −0.30861 1.94E−22 6.38E−21 −0.3717938 −0.3139512 Oaz1 −0.4185288 −0.42629 1.75E−59 1.27E−51 −0.34722806 −0.374798  Ndufb8 −0.3480766 −0.3899 3.81E−17 1.46E−55 −0.34807658 NA Hist1h1c −0.3009065 −0.33105 1.17E−16 5.78E−33 −0.30090653 NA Ces1f −0.31259 −0.53364 1.45E−16  9.25E−112 −0.31258996 NA Slco1a1 −0.3628438 −0.63248 1.36E−29  5.52E−101 −0.36284376 NA Ugt2a3 −0.3334414 −0.5474 8.21E−34 2.33E−87 −0.30752809 −0.3334414 Psmb1 −0.3584824 −0.27157 3.95E−16 5.68E−21 −0.35848235 NA Baat −0.308582 −0.44583 4.31E−16 1.01E−65 −0.308582 NA Bckdha −0.3499796 −0.4047 6.82E−16 2.27E−47 −0.34997961 NA Atp5o −0.3316283 −0.26865 9.93E−16 2.25E−21 −0.33162829 NA C8b −0.3601712 −0.25108 1.12E−72 1.50E−25 −0.31591777  0.31870312 Mrps18c −0.3662911 −0.27427 1.60E−15 1.08E−17 −0.3662911 NA Sdhb −0.2896428 −0.35736 2.09E−15 2.51E−46 −0.28964282 NA Aox3 −0.3333198 −0.42946 2.60E−25 1.72E−66 −0.33331983  0.28784543 Mdh1 −0.3076578 −0.32903 3.99E−15 2.04E−40 −0.30765782 NA Otc −0.2990342 −0.58497 6.99E−15  1.50E−116 −0.29903416 NA Sc4mol −0.3261705 −0.51957 6.26E−23 1.06E−80 −0.32617048 −0.2734797 Igfbp2 −0.3450878 −0.71783 4.02E−44  3.60E−190 −0.29898103 −0.3450878 Rps21 −0.3644509 −0.31687 2.02E−14 2.81E−22 −0.36445087 NA Sar1b −0.3176075 −0.42209 1.79E−35 6.58E−68 −0.30793071 −0.3176075 Slc2a2 −0.3123484 −0.29127 5.54E−60 2.49E−31 −0.31234839 NA Txn1 −0.3091238 −0.27735 2.50E−14 6.45E−28 −0.30912379 NA 0610011F06Rik −0.3036885 −0.28594 2.80E−14 3.51E−28 −0.30368851 NA Slc10a1 −0.3257574 −0.39549 1.24E−84 8.15E−51 −0.32575741 NA Rps10 −0.3369091 −0.25266 4.59E−14 3.85E−13 −0.33690905 NA Esd −0.28076 −0.38154 9.90E−24 1.94E−49 −0.28076002 −0.2537949 Cyp4f14 −0.2959332 −0.28357 1.60E−13 6.47E−28 −0.29593321 NA Dhrs4 −0.3320744 −0.26886 9.59E−13 5.96E−15 −0.33207442 NA Mup2 1 −0.73872 8.16E−38  5.33E−115 −0.50447051 −0.2742436 Selk −0.3383144 −0.27925 1.30E−13 4.58E−18 −0.3383144 NA Rpl14 −0.2776378 −0.35706 7.87E−12 2.16E−37 −0.27763775 NA Ndufs4 −0.3131609 −0.29996 1.01E−11 2.26E−18 −0.31316093 NA Abcd3 −0.2718051 −0.32684 1.44E−11 1.45E−40 −0.27180511 NA Cela1 −0.2722968 −0.25261 1.78E−11 1.03E−30 −0.27229684 NA Sparcl1 −0.253617 −0.25362 3.40E−53 3.78E−57 −0.25361699 −0.253617  Aadat −0.318628 −0.32573 3.04E−11 9.13E−34 −0.31862795 NA Agxt −0.2583834 −0.30383 4.28E−11 1.79E−39 −0.25838339 NA Sigmar1 −0.3054683 −0.28236 7.64E−11 5.67E−17 −0.30546833 NA Psma6 −0.3035366 −0.28171 8.48E−11 2.82E−20 −0.30353658 NA Cyp2c55 −0.2904354 −0.34784 9.36E−11 2.21E−52 −0.29043537 NA Proc −0.2707194 −0.31978 9.66E−11 1.66E−39 −0.27071936 NA Cebpb −0.4715795 −0.30633 2.38E−50 1.73E−23 −0.36173829 −0.4715795 Rpl13 −0.2996936 −0.31461 1.78E−21 7.45E−64 −0.29881609 −0.2996936 Ubb −0.2750304 −0.26377 2.58E−11      0.0138701 −0.27503038 −0.2593394 Rps24 −0.2624737 −0.38646 8.21E−10 6.91E−41 −0.26247367 NA Ppp2r5a −0.2605045 −0.3151 7.14E−52 3.37E−36 −0.26050454 NA Lipc −0.2548415 −0.42306 1.09E−09 3.19E−59 −0.25484148 NA Rabac1 −0.2659872 −0.34206 1.45E−09 3.25E−38 −0.26598721 NA Mvd −0.2704099 −0.32733 1.91E−09 2.22E−59 −0.27040987 NA Zfp683 −0.4216891 −0.42169 1.05E−25 1.10E−47 −0.42168911 −0.421395  Park7 −0.26023 −0.27093 1.55E−56 9.02E−25 −0.26023002 NA Cyp2b10 −1.1644909 −1.25497  9.40E−117  1.74E−217 −0.51746066 −1.1644909 Rpl34 −0.2975985 −0.26459 8.13E−08 1.43E−12 −0.29759854 NA mt-Atp6 −0.573743 −0.91464 1.31E−25  7.98E−137 −0.47818742 −0.573743  Sco2 −0.2928706 −0.39595 1.32E−23 1.04E−49 −0.26050852 −0.2928706 Ndufa5 −0.251989 −0.31028 1.96E−06 4.19E−22 −0.25198899 NA Serpina3c −0.472511 −0.59557 8.19E−59  4.68E−124 −0.28701133 −0.4088789 4931406C07Rik −0.2543636 −0.28178 9.62E−06 3.10E−19 −0.25436363 NA Gstp1 −0.8558314 −0.67166  1.88E−150 4.28E−90 −0.26437467 −0.4301974 Ftl1 1 −0.34781 2.43E−17 4.66E−11 −0.26029441 −0.3497774 mt-Nd2 −1.241926 −1.35078 0 0 NA −1.241926  mt-Nd5 −1.3835911 −1.49646 0 0 NA −1.3835911 mt-Co1 −1.4334276 −1.56995 0 0 NA −1.4334276 mt-Cytb −1.5712329 −1.55403 0 0 NA −1.5712329 mt-Rnr2 −0.778342 −0.96745  5.04E−251 0 NA −0.778342  Serpina1e −0.4026267 −0.27984  7.17E−151 1.24E−63 NA −0.4026267 mt-Rnr1 −0.4853999 −0.87219  1.71E−195 0 NA −0.4562114 Ahcy −0.5629686 −0.49011  6.43E−120  1.57E−115 NA −0.5629686 Serpina1b −0.3017706 −0.29448 4.66E−97 1.99E−74 NA −0.3017706 Ces1d −0.428906 −1.2015 8.07E−91 0 NA −0.428906  Cth −0.5108991 −0.33921 1.34E−76 3.95E−48 NA −0.5108991 Ech1 −0.4291326 −0.50402 5.62E−72  2.34E−114 NA −0.4291326 Ephx2 −0.3693036 −0.5708  3.91E−109  1.49E−121 NA −0.3693036 mt-Nd6 −0.4778511 −0.68551 1.67E−57  2.74E−110 NA −0.4778511 Cyp2d10 −0.3231514 −0.32533 1.31E−55 3.76E−49 NA −0.3231514 Clpx −0.4047356 −0.41084 1.07E−46 1.11E−53 NA −0.4047356 Gm4076 −0.3254694 −0.34583 2.57E−39 7.98E−74 NA −0.3254694 Acot1 0.30784004 −0.29933  1.49E−100 2.65E−38 −0.28863865 −0.2862042 Gm5096 −0.3630891 −0.39955 1.95E−32 4.99E−39 NA −0.3630891 Gas5 −0.3361532 −0.29842 2.74E−31 6.31E−32 NA −0.3361532 Mup20 −0.4762073 −1.23782  3.88E−128 0 NA −0.2818717 Akr1c19 −0.2726671 −0.38253 7.78E−21 1.32E−46 NA −0.2726671 Eci1 −0.2763831 −0.31335 2.48E−20 3.71E−30 NA −0.2763831 Fcgrt −0.2693142 −0.27095 4.12E−64 1.81E−26 NA −0.2693142 Gm20594 −0.3600006 −0.57378 1.55E−09 4.48E−60 0.295686612 −0.3600006 Eef1b2 −0.3173232 −0.36733 2.36E−38 1.90E−45 NA NA Rps8 −0.2746013 −0.27985 8.37E−12 2.52E−16 NA NA C6 −0.2669877 −0.2551 3.03E−10 2.04E−21 NA NA A48A96logFC A6p A24p A48A96p PH3logFC Mup11 −1.6211346  1.04E−235 0 0 −0.976756 Mup19 −1.7308682  4.33E−227 0 0 −2.932276 Mup17 −2.0963504  1.37E−209 0 0 −2.514473 Fabp1 NA  1.10E−198 NA NA NA Akr1c6 −0.4689885  2.54E−187 2.86E−52  8.38E−143 −0.434922 Mgst1 NA  2.13E−181 NA NA −0.322743 Mup9 −1.9358842  9.10E−177 0 0 −2.453597 Apoc1  0.39209541  1.40E−171  2.01E−117  7.90E−242 NA Mup16 −1.1006815  1.22E−168  2.06E−200 0 −0.848727 Adh1 NA  1.90E−167 8.71E−80 NA −0.295981 Cyp2e1 NA  4.79E−166 3.18E−51 NA −0.301498 Gpx1 NA  9.80E−161  6.77E−238 NA NA Mup3 −0.379596   1.31E−157 0  7.73E−237 −0.52641  Mup18 −1.59087   4.19E−157 0 0 −2.617739 Apoc4 NA  9.54E−150  3.56E−114 NA −0.356086 Mup6 −2.0320849  2.16E−149  1.18E−255 0 −2.386597 Nudt7 −1.1415754  1.44E−129 NA  2.67E−255 NA Mup12 −0.767699   4.63E−127 NA  1.14E−185 −0.589619 Car3 −0.4053086  1.61E−124 NA  4.54E−111 NA Apoa2 NA  6.54E−122 0 NA NA Selenbp2 −1.190222   6.93E−118 5.26E−63 0 NA 2810007J24Rik NA  6.76E−113 NA NA NA Uqcrq NA  4.23E−106  1.50E−140 NA −0.316452 Ttr  0.38890744  3.44E−101 NA  5.79E−264 NA Cyp2c29 NA 1.97E−99 2.74E−69 NA −1.027268 Tmem205 NA 1.21E−96 1.05E−96 NA NA Gsta3 NA 6.16E−95  2.44E−166 NA −0.537842 Cyb5 NA 7.09E−94  8.36E−212 NA −0.719657 Hsd3b7 −0.3827383 3.79E−93 2.93E−47 1.78E−61 −0.451728 Acaa1b NA 9.23E−93  4.51E−247 NA −0.263859 Gm13775 −1.0780882 3.12E−88  3.97E−187  1.37E−292 −1.255657 Psen2 NA 1.77E−85 NA NA −0.419556 Mup15 −1.2612126 1.10E−84  1.08E−153  1.22E−233 −1.07441  Cyp8b1  0.28231507 6.32E−84 8.76E−88 3.14E−45 −0.364571 Rps27l NA 1.39E−81 5.43E−90 NA −0.361139 Cox6c NA 3.24E−81 2.39E−77 NA −0.411283 Ugt2b5 NA 3.90E−81  9.60E−175 NA −0.423085 Hsd3b5 −0.8301459 2.04E−80 NA  1.41E−154 −0.587529 Cyp2a5 NA 3.74E−79 3.04E−57 NA −0.938183 Ugt2b1 NA 2.28E−76 4.20E−34 NA NA Cyp1a2 −0.4457662 1.08E−75 NA 2.09E−66 −0.48192  Hgd NA 1.96E−75 NA NA NA Adck3 NA 2.27E−75 6.63E−24 NA −0.48294  Mup21 −1.0081719 2.40E−75  2.15E−121 0 −0.668771 Cyp2d9 NA 2.15E−73  3.96E−157 NA NA Apoe  0.4072569 3.19E−71  3.30E−238 0 −0.262098 mt-Nd4 −0.9364059 7.92E−71 0 0 −1.630375 C8g NA 3.81E−68 4.13E−96 NA NA Mup7 −1.1155878 1.78E−67 NA 0 −0.293978 Ubc NA 4.04E−67 2.42E−49 NA −0.273243 Pon1 NA 1.66E−66 5.87E−44 NA −0.302819 Oaf  0.40356761 4.77E−65 NA  1.03E−122 −0.333767 Ugt2b36 NA 1.36E−63 1.07E−57 NA −0.287193 Ces3a NA 1.00E−62 5.80E−77 NA NA Mup5 −1.3518107 1.04E−61  6.49E−171  1.94E−240 −1.484561 Ndufa4 NA 1.11E−61 3.70E−65 NA NA Hagh NA 1.62E−61 NA NA NA Cyp3a11  0.31392733 1.90E−61  1.05E−122  2.07E−107 −0.25122  Hsd3b3 −0.2996621 1.98E−61 NA 3.00E−20 NA Hint1 NA 4.75E−61 1.71E−80 NA NA Scp2 −0.3251618 1.05E−60 NA  3.33E−100 −0.279911 Cox4i1 NA 5.83E−60  4.62E−112 NA −0.288035 Sod1 NA 7.55E−60 3.30E−72 NA NA Hacl1 NA 1.20E−59 NA NA −0.3329  Hpd NA 2.47E−59 1.72E−56 NA NA mt-Co2 −0.9187845 3.38E−58  7.79E−219  1.79E−173 −1.341687 Cyp2c37 NA 9.93E−57 9.75E−56 NA −0.662336 Inmt −0.2532218 1.21E−55 1.57E−51 7.77E−21 −0.308364 Uox NA 6.13E−55 NA NA NA Uqcr11 NA 1.37E−54 5.87E−27 NA NA Ankrd55 −0.9742804 1.82E−54  4.38E−235 1.45E−68 −1.464696 Prdx1 −0.3618909 7.29E−52 1.94E−38 1.10E−92 NA Hebp1 NA 1.18E−51 NA NA −0.313009 Cox7b NA 3.42E−51 4.55E−23 NA −0.304639 mt-Nd1 −0.5916468 2.80E−49 0  5.29E−267 −1.136737 Cox7a2 NA 2.00E−48 5.69E−35 NA NA Chchd2 NA 2.39E−48 7.88E−56 NA NA Rarres2 NA 3.29E−48 1.17E−31 NA NA Ndufa6 NA 4.43E−48 4.71E−27 NA −0.252724 Rdh7  0.36416156 7.41E−48 1.69E−54  6.63E−181 NA Pah NA 1.25E−47 NA NA NA Leap2 NA 1.25E−47 1.45E−22 NA NA Cyp7b1 −0.5424035 4.96E−47 NA 3.09E−98 NA Cyp2c50 NA 2.92E−46 1.48E−24 NA −0.763912 Mup4 −0.9531018 1.26E−43  1.96E−121  9.25E−125 −1.805302 Cml1 NA 1.70E−43 2.10E−29 NA −0.27734  Aadac NA 4.18E−43 5.65E−43 NA NA Mup13 −0.5525594 8.39E−43 2.45E−76 6.20E−45 −0.755608 Ttc39c −0.3745045 2.03E−42 NA 2.88E−40 NA Aldh1a1 NA 1.02E−41 NA NA −0.402451 Ddt NA 1.48E−41 1.33E−60 NA NA Cox6a1  0.29212877 1.69E−41 9.18E−60 1.78E−87 NA Atp5j2 NA 3.32E−40 NA NA NA Ndufb2  0.2515952 5.29E−40 2.52E−28 1.66E−45 NA Ndufb9 NA 5.48E−40 NA NA NA Atp5h  0.43416354 8.64E−40 7.16E−69  1.41E−124 −0.351854 Qdpr NA 1.45E−39 NA NA NA Atp5f1 NA 2.05E−39 1.01E−28 NA NA Serpina1a NA 8.08E−39  4.32E−247 NA NA Fabp2 NA 4.18E−38 3.19E−36 NA NA Khk  0.31010387 3.36E−37 4.03E−35 1.03E−67 NA Mpc2 NA 7.20E−37 NA NA −0.268047 Ndufb6 NA 4.30E−35 4.45E−28 NA −0.311203 Elovl3 −0.4426528 4.74E−35  6.30E−121 5.92E−91 −0.252293 Arl4d NA 6.71E−35 NA NA −0.32852  Akr1c14 NA 1.08E−34 NA NA NA Csad NA 1.25E−34 1.92E−72 NA NA Ndufb11 −0.275646  3.19E−34 8.28E−53 4.56E−22 −0.367923 Cox5b NA 4.68E−34 1.67E−32 NA NA Rplp1 NA 4.91E−34 5.94E−23 NA NA Fxyd1 NA 2.89E−33 3.83E−34 NA NA Atp5j NA 3.59E−33 NA NA NA Rpl32 −0.2846892 1.10E−32 2.90E−16 8.16E−20 NA Dio1 NA 1.11E−32 NA NA NA Nit2 NA 4.49E−32 NA NA NA Gnmt NA 1.40E−31  1.33E−133 NA NA Ssr4 NA 1.87E−31 NA NA NA Ndufs6 NA 2.00E−31 4.72E−31 NA NA Etfb NA 4.01E−31 NA NA NA Rsp14 −0.3484055 1.50E−30 3.26E−44 1.07E−73 −0.346341 Blvrb NA 6.23E−30 NA NA NA Uqcr10 NA 2.60E−29 NA NA NA Cyp3a25  0.31857327 1.37E−27 NA  1.19E−134 −0.410512 Mup8 −0.795757  2.07E−27 4.14E−25  1.23E−114 −0.793731 Sc5d NA 2.09E−27 3.57E−48 NA NA Adipor2 NA 3.14E−27 NA NA NA Rpl36a1 NA 1.26E−26 NA NA NA Serpina1e −0.6620459 1.97E−26 8.67E−65 0 NA Serpina1d NA 2.07E−26  1.74E−184 NA NA Dcxr NA 2.61E−26 2.61E−43 NA −0.27134  Cmbl NA 2.71E−26 1.48E−28 NA NA Ndufb4 NA 2.93E−26 3.64E−28 NA NA B2m NA 5.62E−26  1.86E−102 NA NA Cyp4a12a −0.2770512 6.69E−26 NA 7.00E−24 −0.259776 Hspe1 −0.2813189 9.37E−26 1.53E−19 1.46E−15 NA Uqcrh NA 1.41E−25 NA NA NA mt-Co3 −0.9151085 1.72E−25  9.57E−168  4.34E−176 −1.233962 Minos1 NA 2.00E−25 NA NA NA Mup14 −0.7607669 2.00E−25 NA 2.64E−96 −0.34089  Cfhr2 −0.3063257 4.83E−25 4.87E−29 2.09E−34 NA Timm13 NA 2.46E−24 NA NA NA 1500017E21Rik NA 2.47E−24 NA NA NA Hint2 NA 5.24E−24 6.90E−37 NA −0.29931  Pbld1  0.3226882 7.81E−24 NA 4.53E−92 NA Glo1 NA 1.87E−23 NA NA NA Rpl13a NA 3.58E−22 NA NA −0.314606 Ces3b −0.2632928 6.63E−22 1.58E−25 5.30E−27 NA Rps18 NA 8.18E−22 NA NA −0.269207 Serpina12 −0.324744  1.67E−21 NA 2.90E−24 NA Ndufa2 NA 2.46E−21 NA NA NA Mup1 −0.5568369 2.63E−21 1 7.40E−25 −0.490972 Bphl NA 5.02E−21 NA NA NA Prdx4 −0.2519751 1.27E−20 6.96E−24 8.80E−10 NA Cyp2c54  0.25038702 1.78E−20 3.25E−32 9.37E−37 −0.71286  Rps2 −0.3742466 2.13E−20 6.76E−40 5.09E−44 −0.442508 Acsl1  0.25633542 2.16E−20 1.40E−54 1.12E−70 NA Cebpa NA 3.89E−20 NA NA −0.260692 Uqcrb NA 6.59E−20 NA NA NA 1110008F13Rik NA 2.46E−19 4.13E−58 NA NA Tmem243 NA 2.52E−19 2.35E−20 NA NA Atp5g3 NA 4.43E−19 NA NA NA Rps15 NA 4.49E−19 7.79E−24 NA NA Nme1 −0.2857051 5.43E−19 NA 4.26E−14 NA Timm8b NA 8.39E−19 NA NA NA Ndufc2 NA 1.31E−18 1.02E−18 NA NA S100a1 NA 1.68E−18 1.76E−35 NA NA Sdhd  0.32084192 2.07E−18 NA 8.20E−61 NA Usmg5  0.27873092 2.85E−18 NA 4.55E−56 NA Cyp27a1 NA 3.99E−18 4.44E−19 NA NA Rps3 NA 5.25E−18 NA NA NA Slc22a30 −0.2954008 5.26E−18 NA 1.34E−16 NA Rps9 NA 1.65E−17 1.94E−22 NA NA Oaz1 −0.4185288 1.73E−17 8.14E−43 1.75E−59 −0.339005 Ndufb8 NA 3.81E−17 NA NA NA Hist1h1c NA 1.17E−16 NA NA −0.331046 Ces1f NA 1.45E−16 NA NA NA Slco1a1 −0.2956402 2.16E−16 NA 1.36E−29 NA Ugt2a3 NA 3.75E−16 8.21E−34 NA NA Psmb1 NA 3.95E−16 NA NA NA Baat NA 4.31E−16 NA NA NA Bckdha NA 6.82E−16 NA NA NA Atp5o NA 9.93E−16 NA NA NA C8b −0.3601712 1.33E−15 1.74E−50 1.12E−72 NA Mrps18c NA 1.60E−15 NA NA NA Sdhb NA 2.09E−15 NA NA NA Aox3 NA 2.16E−15 2.60E−25 NA −0.275389 Mdh1 NA 3.99E−15 NA NA NA Otc NA 6.99E−15 NA NA NA Sc4mol NA 7.58E−15 6.26E−23 NA NA Igfbp2 NA 1.25E−14 4.02E−44 NA −0.348404 Rps21 NA 2.02E−14 NA NA NA Sar1b NA 2.07E−14 1.79E−35 NA NA Slc2a2  0.27229797 2.36E−14 NA 5.54E−60 NA Txn1 NA 2.50E−14 NA NA NA 0610011F06Rik NA 2.80E−14 NA NA NA Slc10a1  0.31432581 3.37E−14 NA 1.24E−84 NA Rps10 NA 4.59E−14 NA NA NA Esd NA 1.14E−13 9.90E−24 NA −0.302906 Cyp4f14 NA 1.60E−13 NA NA NA Dhrs4 NA 9.59E−13 NA NA NA Mup2 −0.5530585 9.59E−13 1 8.16E−38 −0.650107 Selk −0.2893006 1.79E−12 NA 1.30E−13 NA Rpl14 NA 7.87E−12 NA NA −0.261157 Ndufs4 NA 1.01E−11 NA NA NA Abcd3 NA 1.44E−11 NA NA NA Cela1 NA 1.78E−11 NA NA NA Sparcl1 −0.253617  2.56E−11 1.01E−31 3.40E−53 −0.253617 Aadat NA 3.04E−11 NA NA NA Agxt NA 4.28E−11 NA NA NA Sigmar1 NA 7.64E−11 NA NA −0.282365 Psma6 NA 8.48E−11 NA NA NA Cyp2c55 NA 9.36E−11 NA NA −0.316565 Proc NA 9.66E−11 NA NA NA Cebpb NA 9.79E−11 2.38E−50 NA NA Rpl13 NA 1.55E−10 1.78E−21 NA −0.314606 Ubb −0.2644328 6.19E−10 2.58E−11      0.12064603 −0.263774 Rps24 NA 8.21E−10 NA NA NA Ppp2r5a  0.25089771 9.42E−10 NA 7.14E−52 −0.263514 Lipc NA 1.09E−09 NA NA NA Rabac1 NA 1.45E−09 NA NA NA Mvd NA 1.91E−09 NA NA −0.327327 Zfp683 NA 5.25E−09 1.05E−25 NA −0.421689 Park7  0.25151769 5.75E−09 NA 1.55E−56 NA Cyp2b10 NA 2.09E−08  9.40E−117 NA −1.254972 Rpl34 NA 8.13E−08 NA NA NA mt-Atp6 −0.3234264 1.61E−07 1.31E−25 3.18E−23 −0.852556 Sco2 NA 5.95E−07 1.32E−23 NA NA Ndufa5 NA 1.96E−06 NA NA NA Serpina3c −0.472511  7.83E−06 1.55E−34 8.19E−59 −0.554657 4931406C07Rik NA 9.62E−06 NA NA NA Gstp1 −0.8558314 0.00132565 1.39E−27  1.88E−150 NA Ftl1 −0.2988085 0.34648571 2.43E−17 1 −0.346327 mt-Nd2 −0.8980548 NA 0 0 −1.128777 mt-Nd5 −0.7991472 NA 0  7.18E−267 −1.145551 mt-Co1 −1.0433076 NA 0 0 −1.381308 mt-Cytb −0.8545555 NA 0 0 −1.296044 mt-Rnr2 −0.5594463 NA  5.04E−251  1.98E−232 −0.873558 Serpina1e NA NA  7.17E−151 NA NA mt-Rnr1 −0.4853999 NA  2.01E−123  1.71E−195 −0.872187 Ahcy NA NA  6.43E−120 NA −0.375628 Serpina1b NA NA 4.66E−97 NA NA Ces1d  0.28525464 NA 8.07E−91 7.83E−69 −0.385155 Cth NA NA 1.34E−76 NA −0.308848 Ech1  0.2504813 NA 5.62E−72 1.35E−56 NA Ephx2  0.28125856 NA 3.71E−68  3.91E−109 NA mt-Nd6 NA NA 1.67E−57 NA −0.515107 Cyp2d10 NA NA 1.31E−55 NA NA Clpx NA NA 1.07E−46 NA −0.306093 Gm4076 −0.3083212 NA 1.37E−35 2.57E−39 −0.342158 Acot1  0.30784004 3.05E−10 5.23E−33  1.49E−100 NA Gm5096 NA NA 1.95E−32 NA −0.399548 Gas5 NA NA 2.74E−31 NA NA Mup20 −0.4762073 NA 9.36E−26  3.88E−128 NA Akr1c19 NA NA 7.78E−21 NA NA Eci1 NA NA 2.48E−20 NA NA Fcgrt  0.25847884 NA 8.21E−19 4.12E−64 NA Gm20594 −0.3565586 1.60E−05 2.58E−08 1.55E−09 −0.559578 Eef1b2 −0.3173232 NA NA 2.36E−38 NA Rps8 −0.2746013 NA NA 8.37E−12 NA C6 −0.2669877 NA NA 3.03E−10 NA PH48logFC PH120logFC PH3p PH48p PH120p Mup11 −1.41509233 −1.769207 0 0 0 Mup19 −3.63217051 −3.348976 0 0 0 Mup17 −2.2696211  −2.382124 0 0 0 Fabp1 −0.54216735 −0.826492 NA  8.21E−214 0 Akr1c6 −0.50114352 −0.457642  6.85E−150  1.04E−103  3.18E−123 Mgst1 −0.28624093 −0.368754  2.50E−131 3.71E−58  2.20E−129 Mup9 −2.21914429 −2.520659 0 0 0 Apoc1 −0.31073779 NA NA 1.04E−90 NA Mup16 −0.87654486 −1.245137  1.76E−222  2.12E−149 0 Adh1 NA NA  3.27E−106 NA NA Cyp2e1 −0.29860874 0.2969  4.23E−36 2.45E−19 6.94E−06 Gpx1 −0.32198413 NA NA  2.36E−120 NA Mup3 −1.4237591  −1.310718 0 0 0 Mup18 −2.37334874 −2.585635 0 0 0 Apoc4 NA −0.50176   2.38E−146 NA  1.19E−182 Mup6 −2.64537347 −2.588052 0 0 0 Nudt7 −0.56604376 NA NA 9.48E−52 NA Mup12 −1.21051737 −1.228078  2.77E−105  1.10E−243 0 Car3 −1.29219188 −1.168631 NA  2.01E−301 0 Apoa2 −0.61598119 −0.427739 NA 0  1.04E−276 Selenbp2 −0.8571994  −0.354512 NA  9.70E−194 5.81E−73 2810007J24Rik −1.09399829 −0.337773 NA  2.63E−273 7.72E−74 Uqcrq −0.34186946 −0.485355 1.28E−72 1.11E−51  2.42E−124 Ttr −0.28613839 NA NA 3.87E−82 NA Cyp2c29 NA −0.997503  2.76E−235 NA  3.62E−184 Tmem205 −0.36376261 NA NA 6.01E−57 NA Gsta3 −0.57982304 −0.796927  2.50E−189  2.50E−118  3.08E−250 Cyb5 −0.48647684 −0.751689 0  1.24E−108  2.13E−288 Hsd3b7 −0.58164214 NA 3.52E−87 5.15E−93 NA Acaa1b −0.74247809 −0.855527 2.20E−79  8.89E−175 0 Gm13775 −1.14521098 −1.171528 0  3.97E−216  5.37E−288 Psen2 NA NA 1.69E−77 NA NA Mup15 −1.3641826  −1.359329  5.07E−136  2.34E−202  5.96E−268 Cyp8b1 −0.56548352 −0.59929  3.21E−55 1.09E−90  1.54E−120 Rps27l −0.37756614 −0.645823 1.30E−60 7.98E−50  1.42E−139 Cox6c −0.51741711 −0.610223 1.20E−74 4.59E−79  2.30E−132 Ugt2b5 −0.68326299 −0.716337  8.09E−193  1.47E−190  5.77E−289 Hsd3b5 −0.88646345 −0.50626  1.00E−67  3.58E−129 4.13E−58 Cyp2a5 −0.52568008 −0.869525  8.06E−111 1.48E−38 1.93E−69 Ugt2b1 −0.72210229 −0.261758 NA  5.69E−140 1.59E−33 Cyp1a2 NA −0.284567 3.86E−66 NA 8.09E−18 Hgd −0.2739982  NA NA 2.46E−30 NA Adck3 −0.56969289 NA 4.38E−91 6.36E−82 NA Mup21 −1.34664515 −1.637812  6.47E−176  1.32E−290 0 Cyp2d9 −0.61667658 −0.325039 NA  8.72E−151 1.56E−76 Apoe −0.61588295 NA  3.58E−191 0 NA mt-Nd4 −1.67314023 −1.953206 0 0 0 C8g −0.45563856 NA NA 2.41E−80 NA Mup7 −0.84772673 −0.844128     0.067179  2.63E−114  8.04E−142 Ubc NA NA 3.58E−41 NA NA Pon1 −0.42825679 −0.326048 2.10E−60 1.97E−64 2.43E−57 Oaf NA NA 3.11E−47 NA NA Ugt2b36 −0.62967111 −0.355796 5.82E−81  1.10E−145 4.78E−87 Ces3a −0.72100816 NA NA  1.41E−206 NA Mup5 −1.76898765 −1.77461  0  2.08E−280 0 Ndufa4 −0.4035957  −0.512723 NA 1.02E−52  4.13E−107 Hagh −0.28843067 −0.398106 NA 2.99E−32 4.45E−73 Cyp3a11 NA −0.803553  8.18E−135 NA 0 Hsd3b3 −0.34746055 NA NA 3.82E−42 NA Hint1 NA −0.487016 NA NA  9.22E−101 Scp2 −0.31951947 NA  5.16E−159 1.15E−50 NA Cox4i1 −0.57523009 −0.518813 5.97E−88  2.44E−141  2.23E−168 Sod1 −0.27785367 −0.483374 NA 1.68E−63  3.17E−216 Hacl1 NA −0.294917 4.71E−52 NA 2.73E−36 Hpd −0.31794334 NA NA 2.00E−54 NA mt-Co2 −1.41732822 −1.394736 0  5.51E−209  1.21E−274 Cyp2c37 −0.41293867 −0.820386  4.16E−114 1.60E−40  2.10E−130 Inmt −0.50241447 −0.67979  9.17E−37 1.61E−65  1.56E−139 Uox −0.48042234 NA NA 1.42E−89 NA Uqcr11 NA −0.368071 NA NA 8.58E−61 Ankrd55 −1.95094236 −1.470506  6.28E−208  2.52E−247  4.09E−185 Prdx1 NA −0.353764 NA NA 2.27E−73 Hebp1 −0.29746423 −0.274169 1.26E−40 8.29E−32 3.96E−26 Cox7b −0.38652422 −0.650086 6.26E−37 1.05E−43  3.36E−144 mt-Nd1 −1.15463044 −1.543996 0 0 0 Cox7a2 NA −0.441102 NA NA 3.27E−59 Chchd2 −0.36975589 −0.518624 NA 1.70E−48  1.10E−119 Rarres2 −0.49201391 NA NA 1.76E−89 NA Ndufa6 −0.33096547 −0.418445 8.39E−24 3.11E−32 3.80E−59 Rdh7 −0.49691067 NA NA  5.58E−132 NA Pah −0.37985387 NA NA 8.65E−60 NA Leap2 NA −0.404793 NA NA 1.27E−50 Cyp7b1 −0.43815806 NA NA 1.37E−54 NA Cyp2c50 −0.46729844 −0.51653   8.52E−186 1.54E−52 2.38E−78 Mup4 −1.94564614 −1.909428 0 0 0 Cml1 −0.47269345 NA 2.15E−27 5.55E−63 NA Aadac −0.74734282 −0.466443 NA  6.76E−122 6.31E−69 Mup13 −0.87097239 −0.875079  4.35E−116  1.89E−127  6.29E−165 Ttc39c −0.28961231 NA NA 2.34E−27 NA Aldh1a1 NA NA  1.39E−102 NA NA Ddt NA −0.345839 NA NA 1.40E−46 Cox6a1 −0.39061791 −0.275277 NA 1.67E−61 4.29E−41 Atp5j2 −0.25505171 −0.409577 NA 2.55E−25 3.23E−66 Ndufb2 NA −0.336856 NA NA 1.21E−30 Ndufb9 −0.29191091 −0.483703 NA 2.15E−38  1.07E−104 Atp5h −0.35236298 −0.555499 4.84E−19 7.17E−29 7.99E−68 Qdpr −0.31659518 NA NA 1.80E−33 NA Atp5f1 −0.46070987 −0.428497 NA 1.11E−68 1.10E−77 Serpina1a −0.35536875 −0.295263 NA 3.38E−75 6.23E−81 Fabp2 −0.48853359 −0.527187 NA 5.45E−64 2.63E−76 Khk −0.53015038 NA NA 8.89E−91 NA Mpc2 NA −0.39521  4.77E−43 NA 2.71E−68 Ndufb6 −0.47916274 −0.518385 1.04E−35 4.11E−68 3.96E−85 Elovl3 −0.8122507  −0.924846 2.20E−32  1.80E−150  1.57E−229 Arl4d −0.28894161 NA 5.36E−30 3.05E−26 NA Akr1c14 NA −0.280169 NA NA 1.20E−21 Csad −0.30870307 −1.214863 NA 4.35E−30  5.27E−267 Ndufb11 −0.39861879 −0.479045 4.92E−46 7.18E−49 2.10E−70 Cox5b −0.39369185 −0.373464 NA 3.39E−45 5.23E−43 Rplp1 NA −0.274821 NA NA 6.89E−20 Fxyd1 −0.27342229 NA NA 2.95E−25 NA Atp5j −0.30264483 −0.415381 NA 4.96E−37 7.16E−66 Rpl32 NA −0.498593 NA NA 4.42E−73 Dio1 −0.46973235 NA NA 9.15E−59 NA Nit2 −0.25532127 NA NA 6.79E−25 NA Gnmt NA −0.288175 NA NA 8.65E−84 Ssr4 NA −0.283161 NA NA 7.71E−23 Ndufs6 NA −0.341035 NA NA 2.06E−29 Etfb NA −0.270014 NA NA 4.81E−54 Rsp14 NA −0.607508 1.86E−83 NA  3.76E−152 Blvrb NA −0.351075 NA NA 2.20E−30 Uqcr10 NA −0.382322 NA NA 1.93E−47 Cyp3a25 −0.34306526 −0.416457  5.44E−129 2.32E−54 4.60E−99 Mup8 −0.82995644 −0.827182  9.31E−106 3.77E−91  3.80E−123 Sc5d NA −0.274286 NA NA 3.96E−19 Adipor2 −0.25255116 NA NA 1.11E−22 NA Rpl36a1 NA −0.331845 NA NA 3.44E−26 Serpina1e −0.3083608  −0.725197 NA 1.15E−71 0 Serpina1d −0.58685276 NA NA  5.86E−199 NA Dcxr NA NA 1.59E−18 NA NA Cmbl −0.26536599 NA NA 9.66E−25 NA Ndufb4 NA −0.331688 NA NA 2.14E−33 B2m −0.43085129 NA NA 2.11E−97 NA Cyp4a12a −0.4760363  NA 1.18E−52 1.00E−65 NA Hspe1 NA −0.25791  NA NA 3.13E−12 Uqcrh −0.29025996 −0.483114 NA 1.52E−28 5.89E−83 mt-Co3 −1.21238839 −1.229639  1.47E−287  9.73E−175  3.03E−229 Minos1 NA −0.308404 NA NA 8.00E−23 Mup14 −0.49742727 −0.741009 1 2.38E−27 8.52E−68 Cfhr2 −0.63061767 −0.42885  NA 7.59E−98 1.02E−63 Timm13 NA −0.266268 NA NA 1.44E−18 1500017E21Rik −0.51793022 NA NA 1.93E−69 NA Hint2 −0.37377357 −0.333604 6.95E−27 2.60E−44 3.41E−32 Pbld1 −0.26462773 NA NA 2.23E−23 NA Glo1 −0.37923349 −0.317339 NA 3.51E−47 1.59E−34 Rpl13a NA −0.480174 7.45E−64 NA 2.24E−99 Ces3b −0.81955869 NA NA  6.86E−161 NA Rps18 NA −0.415076 5.39E−06 NA 1.19E−34 Serpina12 −0.61236747 −0.404557 NA 7.52E−89 1.92E−45 Ndufa2 NA −0.308306 NA NA 9.67E−23 Mup1 −0.62326727 −0.882907     0.022977 1.11E−33 1.78E−91 Bphl −0.29947816 NA NA 1.70E−33 NA Prdx4 −0.37802456 −0.339425 NA 3.39E−40 1.74E−28 Cyp2c54 −0.54296022 −0.632023  1.75E−163 2.37E−77  1.42E−114 Rps2 −0.26932139 −0.47452  4.24E−69 2.20E−20 3.26E−67 Acsl1 −0.56803038 −0.41703  NA  3.63E−104 1.27E−85 Cebpa −0.48161118 NA 6.82E−18 2.92E−66 NA Uqcrb −0.33950492 −0.359657 NA 1.34E−31 6.07E−33 1110008F13Rik −0.28445851 −0.327483 NA 3.77E−30 1.42E−34 Tmem243 NA −0.275109 NA NA 2.06E−22 Atp5g3 −0.30227788 −0.357248 NA 2.31E−44 1.87E−78 Rps15 NA −0.324543 NA NA 3.43E−16 Nme1 NA −0.291609 NA NA 9.48E−21 Timm8b NA −0.250989 NA NA 2.42E−15 Ndufc2 −0.3708899  −0.371343 NA 1.56E−33 9.91E−31 S100a1 −0.35554448 NA NA 2.21E−35 NA Sdhd NA −0.302303 NA NA 2.47E−32 Usmg5 NA −0.283655 NA NA 1.10E−10 Cyp27a1 −0.32622809 NA NA 1.46E−36 NA Rps3 NA −0.339904 NA NA 7.09E−57 Slc22a30 −0.33187075 −0.257369 NA 7.77E−38 2.47E−15 Rps9 NA −0.30861  NA NA 6.38E−21 Oaz1 −0.42628615 −0.327014 2.14E−37 1.27E−51 1.67E−31 Ndufb8 NA −0.389897 NA NA 1.46E−55 Hist1h1c NA NA 5.78E−33 NA NA Ces1f −0.45903711 −0.533639 NA 9.66E−67  9.25E−112 Slco1a1 −0.63247791 −0.542408 NA  5.52E−101 6.62E−92 Ugt2a3 −0.54739922 −0.457903 NA 2.33E−87 2.95E−72 Psmb1 NA −0.271575 NA NA 5.68E−21 Baat −0.4458331  −0.265815 NA 1.01E−65 1.48E−26 Bckdha −0.4047029  NA NA 2.27E−47 NA Atp5o NA −0.268645 NA NA 2.25E−21 C8b −0.25108437 NA NA 1.50E−25 NA Mrps18c NA −0.274271 NA NA 1.08E−17 Sdhb −0.35736225 NA NA 2.51E−46 NA Aox3 −0.42946046 NA 1.72E−66 1.23E−58 NA Mdh1 −0.3290258  NA NA 2.04E−40 NA Otc −0.58497243 NA NA  1.50E−116 NA Sc4mol NA −0.519569 NA NA 1.06E−80 Igfbp2 −0.5766821  −0.717833 3.39E−70  8.96E−103  3.60E−190 Rps21 NA −0.316866 NA NA 2.81E−22 Sar1b −0.30189148 −0.422088 NA 4.44E−36 6.58E−68 Slc2a2 −0.29126785 NA NA 2.49E−31 NA Txn1 NA −0.277353 NA NA 6.45E−28 0610011F06Rik −0.28593883 NA NA 3.51E−28 NA Slc10a1 −0.39548808 −0.273026 NA 8.15E−51 4.19E−30 Rps10 NA −0.25266  NA NA 3.85E−13 Esd −0.38153946 −0.33891  9.71E−44 1.94E−49 5.03E−45 Cyp4f14 −0.28356503 NA NA 6.47E−28 NA Dhrs4 NA −0.268863 NA NA 5.96E−15 Mup2 −0.73872198 −0.724059 4.29E−84 2.14E−98  5.33E−115 Selk NA −0.279249 NA NA 4.58E−18 Rpl14 NA −0.357061 2.50E−13 NA 2.16E−37 Ndufs4 NA −0.29996  NA NA 2.26E−18 Abcd3 −0.32683847 NA NA 1.45E−40 NA Cela1 −0.2526112  NA NA 1.03E−30 NA Sparcl1 −0.25361699 −0.253617 3.78E−57 5.97E−29 2.01E−42 Aadat −0.32573171 NA NA 9.13E−34 NA Agxt −0.30382793 NA NA 1.79E−39 NA Sigmar1 NA NA 5.67E−17 NA NA Psma6 NA −0.28171  NA NA 2.82E−20 Cyp2c55 NA −0.347841 6.52E−37 NA 2.21E−52 Proc −0.31977688 NA NA 1.66E−39 NA Cebpb −0.3063305  −0.26767  NA 1.73E−23 3.07E−10 Rpl13 NA −0.282418 7.45E−64 NA 3.52E−17 Ubb NA NA      0.0138701 NA NA Rps24 NA −0.386465 NA NA 6.91E−41 Ppp2r5a −0.31509887 −0.281896 3.57E−15 3.37E−36 3.25E−21 Lipc −0.42305546 NA NA 3.19E−59 NA Rabac1 −0.34206368 −0.27537  NA 3.25E−38 1.41E−19 Mvd NA NA 2.22E−59 NA NA Zfp683 −0.42168911 −0.421689 1.10E−47 7.40E−24 3.13E−35 Park7 −0.27092931 NA NA 9.02E−25 NA Cyp2b10 −0.99521902 −1.247317  1.74E−217 1.18E−87  1.24E−168 Rpl34 NA −0.264586 NA NA 1.43E−12 mt-Atp6 −0.91463545 −0.87589   7.98E−137  3.35E−117  3.13E−134 Sco2 −0.39595151 −0.250105 NA 1.04E−49 3.07E−16 Ndufa5 NA −0.31028  NA NA 4.19E−22 Serpina3c −0.58992683 −0.595568  8.44E−109 8.61E−89  4.68E−124 4931406C07Rik NA −0.281781 NA NA 3.10E−19 Gstp1 NA −0.671665 NA NA 4.28E−90 Ftl1 −0.25915144 −0.347807 3.34E−05 1.49E−07 4.66E−11 mt-Nd2 −1.18941087 −1.350784 0 0 0 mt-Nd5 −1.3978975  −1.496458 0  1.28E−300 0 mt-Co1 −1.3991104  −1.56995  0 0 0 mt-Cytb −1.37831332 −1.554027 0 0 0 mt-Rnr2 −0.51967923 −0.967453 0  2.69E−141 0 Serpina1e −0.27983515 NA NA 1.24E−63 NA mt-Rnr1 NA −0.844781 0 NA 0 Ahcy −0.45598557 −0.490113 1.82E−89 7.46E−73  1.57E−115 Serpina1b −0.29448079 NA NA 1.99E−74 NA Ces1d −0.44528336 −1.201503  2.67E−121 2.43E−81 0 Cth −0.33223411 −0.33921  6.91E−47 4.36E−37 3.95E−48 Ech1 −0.4146748  −0.504022 NA 2.57E−62  2.34E−114 Ephx2 −0.57080098 −0.398908 NA  1.49E−121 1.19E−91 mt-Nd6 −0.56026873 −0.685505 1.57E−69 1.14E−72  2.74E−110 Cyp2d10 −0.32533265 −0.262377 NA 3.76E−49 9.23E−44 Clpx −0.41084084 −0.250587 6.23E−36 1.11E−53 3.74E−21 Gm4076 −0.34582632 −0.342317 7.98E−74 2.87E−41 7.57E−56 Acot1 NA −0.299327 NA NA 2.65E−38 Gm5096 −0.33670416 −0.350535 4.99E−39 1.27E−33 9.38E−37 Gas5 −0.29841752 NA NA 6.31E−32 NA Mup20 −1.23781717 −1.081531 NA 0 0 Akr1c19 NA −0.382533 NA NA 1.32E−46 Eci1 −0.29260681 −0.313353 NA 4.47E−29 3.71E−30 Fcgrt −0.27094541 NA NA 1.81E−26 NA Gm20594 −0.57378119 −0.496964 4.48E−60 1.21E−52 1.33E−34 Eef1b2 NA −0.367328 NA NA 1.90E−45 Rps8 NA −0.279846 NA NA 2.52E−16 C6 −0.25510201 NA NA 2.04E−21 NA

TABLE 15b Shared Upregulated Differentially Expressed Genes ID avg_logFC_APAP avg_log_FC_PH p_va_adj_APAP p_val_adj_PH A6logFC A24logFC Mt2 2.06273693 2.6060431  1.9E−237 0 2.06273693 NA Mt1 2.387707773 2.61085499  3.51E−232 0 2.387707773 0.348193009 Plin2 1.461295758 0.72046308  8.58E−163 0 1.461295758 NA Il1r1 1.244999819 0.99816813  1.47E−162 0 1.244999819 NA Actb 1.059835055 0.45698144  6.06E−159 2.1478E−210 1.059835055 0.38446276  Cdkn1a 1.2152557 0.44932547  2.99E−152  7.064E−169 1.2152557 NA Klf6 0.732407935 0.3616937  1.5E−147 8.0005E−203 0.732407935 NA Txnrd1 1.443578942 0.31497985  1.43E−144 3.22341E−84  1.443578942 0.260866185 Gm26924 1.419027502 1.44535576 0 0 1.16085221 1.419027502 2010003K11Rik 0.588354735 0.37221997  2.61E−131 1.0574E−239 0.588354735 NA Krt18 1.257881489 0.52035408  3.97E−121 5.88314E−34  1.257881489 NA Fga 0.828543313 1.03943259 0 0 0.69335023 0.828543313 Mat1a 1.000433202 0.623735 0 0 0.790765268 NA n-R5-8s1 1.252818829 1.2895985 0 0 0.766100662 1.252818829 Lars2 1.711400221 1.41912906  1.38E−293 0 1.391744455 1.711400221 Myh9 1.160233135 0.63103566  3.1E−107 2.8315E−141 1.160233135 0.6391137  Fgg 0.680530925 0.80932271 0 0 0.615329068 0.680530925 Gm24601 0.984391691 0.92456827  2.17E−275 0 0.46836359 0.984391691 Fgb 0.744973762 0.73951913 0 0 0.646934246 0.744973762 Gm15564 1.820580657 1.48588593  6.31E−292 0 1.443066465 1.820580657 Krt8 1.195874806 0.25227676  1.04E−103       0.182829207 1.195874806 NA Clec4f 1.108180782 0.48733692  2.17E−103 1.7326E−119 1.108180782 NA Apoa4 1.367998503 1.18686306  8.56E−101 3.0126E−137 1.367998503 NA Bcl2l1 0.775118224 0.28031533 1.02E−99 1.1685E−128 0.775118224 NA Serpina3m 0.967441963 0.77905275  1.04E−130 0 0.967441963 NA Rcan1 0.707283787 0.50923987 1.24E−93 4.5798E−279 0.707283787 NA D10Wsu102e 0.58780186 0.25602216 2.09E−90 1.0336E−141 0.58780186 NA Slc39a14 1.012749203 0.83158494 2.25E−81 0 1.012749203 0.323040019 C1qb 0.681679654 0.36130977 1.02E−79 6.3479E−100 0.681679654 NA Tmsb4x 0.780616209 0.34765791 7.99E−79 1.30373E−70  0.780616209 NA Ctss 0.764167083 0.27018313 2.26E−78 2.67839E−57  0.764167083 NA Mrap 0.884099926 0.28097461 2.65E−73 1.03675E−10  0.884099926 NA Hnf4a 0.879108718 0.64419525 3.56E−83 5.6829E−290 0.879108718 0.454905579 Csf1r 0.704458586 0.28468437  4.7E−70 3.78986E−37  0.704458586 NA Trp53inp1 1.008414088 0.2692784 1.52E−67 1.01347E−72  1.008414088 0.367960906 Nop58 0.663449653 0.25756665 2.13E−65 1.11973E−93  0.663449653 NA Mfsd2a 0.666142747 0.49635188  5.34E−233 1.6404E−219 0.666142747 NA Lyz2 0.732183369 0.40273572 2.49E−63 3.32908E−93  0.732183369 NA Bach1 0.832333098 0.53323737 2.51E−63 5.5373E−247 0.832333098 NA Fam134b 0.893562894 0.86557818 5.02E−63 0 0.893562894 NA Cd5l 0.693485826 0.49371428 1.08E−62 4.6843E−138 0.693485826 NA Serpina3n 0.848313239 1.75975894 9.93E−85 0 0.848313239 0.413696164 Apob 0.580156235 0.50539758 4.36E−68  8.048E−169 0.580156235 0.4272457  Eif1a 0.795281298 0.29521995  1.8E−60 7.80345E−96  0.795281298 NA Epas1 0.775763153 0.38425941 7.57E−60 2.1215E−138 0.775763153 NA Sdc4 0.619597869 0.43560504 9.47E−59 2.7024E−193 0.619597869 NA C3 0.449521065 1.07195093  1.23E−125 0 0.44276078 0.449521065 Wfdc17 0.486653465 0.31732989 2.57E−58 1.3239E−101 0.486653465 NA Fkbp5 0.516128063 0.66330484 1.44E−57 0 0.516128063 NA Btg2 0.832086378 0.77268683 3.81E−56 7.2437E−290 0.832086378 NA Tiparp 0.545567123 0.48912215 8.73E−55 7.0657E−236 0.545567123 NA Cldn14 0.364540783 0.51158353 1.86E−52  4.316E−281 0.364540783 NA Abhd2 0.484366625 0.26724151 1.13E−50 1.29723E−66  0.484366625 NA Picalm 0.754529703 0.27690217 1.39E−50 1.27269E−76  0.754529703 NA Igfbp1 1.058689301 1.2887899 1.68E−50 0 1.058689301 0.316195447 Stat3 0.715400235 0.48390463 2.74E−50 3.5753E−174 0.715400235 0.297428438 Myo1e 0.614341001 0.39945667 9.34E−50 7.8258E−162 0.614341001 NA Tmem87b 0.434399269 0.28833059 1.07E−49 8.7183E−155 0.434399269 NA Slc10a2 0.299006165 0.30563824 2.04E−49  6.538E−197 0.299006165 NA Lcn2 0.412194792 2.39758181 2.72E−49 0 0.412194792 NA Jmjd1c 0.636619821 0.39612601 3.43E−49 1.0512E−144 0.636619821 NA Itih3 0.546240791 1.22302231 1.11E−89 0 0.546240791 0.492908293 Tacc2 0.329332932 0.87762397 3.95E−42 0 0.329332932 NA Eef2 0.525855561 0.32170576 2.71E−41 1.70104E−97  0.525855561 0.270115373 Ptpn1 0.41633121 0.26826323 3.51E−41 6.9212E−130 0.41633121 NA Tnfrsf1a 0.599573483 0.34684503 3.86E−41 3.4204E−112 0.599573483 NA Ddx3x 0.656890035 0.47100162 1.07E−40 1.3581E−155 0.656890035 NA Itih2 0.501091194 0.33671421 3.43E−38 1.5587E−122 0.501091194 0.298659728 St3gal5 0.607639775 0.88276152  1.06E−170 0 0.607639775 NA Abca1 0.724477701 0.50506234 8.81E−38 3.1915E−172 0.724477701 0.439378423 Bcl3 0.289017645 0.41965014 3.63E−37 3.0494E−251 0.289017645 NA Asl 0.558638879 0.29767377  3.45E−117 1.76334E−83  0.558638879 NA Aldob 0.365460648 0.49020085  9.03E−178 0 0.315339576 NA Ugdh 0.633076584 0.26044353 5.17E−34 4.68355E−05  0.633076584 NA H3f3b 0.702914634 0.75556711 7.03E−34 4.4441E−288 0.702914634 NA Xbp1 0.603165814 0.539986 9.59E−34 1.3385E−208 0.603165814 NA Ctsl 0.530101805 0.25652087 1.93E−33 1.56147E−59  0.530101805 NA Hspb8 0.633933124 0.66784725   2E−33 9.1859E−267 0.633933124 NA Eif4g2 0.559692663 0.3843028 1.62E−67  2.505E−110 0.559692663 0.465990267 Epb4.1 0.562789274 0.34943067 1.67E−30 1.9295E−113 0.562789274 NA Rnd3 0.36548808 0.28514768 3.93E−30 4.6581E−134 0.36548808 NA Ddx5 0.522944475 0.25167504  5.9E−30 3.02351E−75  0.522944475 NA Plec 0.467512335 0.26712212  8.3E−30 2.03726E−37  0.467512335 NA Jak1 0.603850485 0.36276669 1.34E−29 2.4382E−103 0.603850485 0.254122657 Errfi1 0.393680047 0.50085053 1.52E−29 7.4336E−262 0.393680047 NA Iigp1 0.768753667 0.30588909 7.59E−66 4.94888E−49  0.768753667 0.454178892 Lrg1 0.490792829 1.26050974 1.37E−62 0 0.490792829 0.436838294 Gpt2 0.539114072 0.53333178 2.49E−28 3.6697E−218 0.539114072 NA Gjb2 0.60822545 0.63950744 3.74E−38 9.9227E−255 0.60822545 0.391136188 Dst 0.510971252 0.32990555 1.75E−35 7.3975E−105 0.510971252 0.324301394 Wbp1l 0.553507326 0.40913816  4.08E−134 1.2925E−127 0.553507326 NA Fn1 0.699634526 1.01877291  1.87E−106 0 0.521230804 0.699634526 Grn 0.540768685 0.40331576  1.07E−154 3.4391E−128 0.540768685 NA Mpeg1 0.493478112 0.54117001  1.8E−24 4.2393E−174 0.493478112 NA Aff4 0.616309327 0.34418622 1.96E−24 7.00106E−97  0.616309327 NA Gm26917 0.823736053 0.47555416 5.26E−54 2.4164E−144 0.60120474 0.823736053 Tns1 0.434939232 0.33981795  8.9E−24 4.5763E−128 0.434939232 NA Arg1 0.317948822 0.38161635 8.62E−23  2.227E−218 0.317948822 NA Arhgef12 0.590764816 0.30486583 8.83E−23 1.49183E−67  0.590764816 0.304679431 Man2a1 0.497115325 0.36999936 2.32E−81 3.60298E−98  0.497115325 0.28327895  Lpgat1 0.595219291 0.40078798 3.53E−63 1.2472E−107 0.595219291 0.394625955 Il6ra 0.304392668 0.25169684 5.08E−20 2.9323E−108 0.304392668 NA Ptp4a1 0.262691158 0.39313737 3.82E−19 6.0997E−190 0.262691158 NA Atp2a2 0.494962728 0.35036327 7.58E−69 8.21385E−94  0.494962728 NA Aass 0.477517138 0.70561534 3.07E−18 1.0663E−286 0.477517138 NA Nedd4l 0.281232817 0.2718271  4.9E−18 1.5124E−116 0.281232817 NA Egr1 0.584558888 0.62048047  2.8E−17 7.2676E−185 0.584558888 NA Litaf 0.394366845 0.39600771 2.04E−16  2.337E−132 0.394366845 NA Plk3 0.416624571 0.48801637 3.12E−16 8.2222E−205 0.416624571 NA Slc41a2 0.278262888 0.44132177 2.13E−34 2.2246E−166 0.260152635 0.278262888 Hsp90ab1 0.322748941 0.45585151 8.34E−16 1.16529E−94  0.322748941 NA Tgm2 0.399330712 0.37123494 1.43E−15 5.49556E−85  0.399330712 NA Shb 0.315236194 0.43061356 4.68E−15 4.0274E−182 0.315236194 NA Tmed5 0.401633325 0.29601878  5.01E−102 1.362E−80 0.401633325 NA Atp1b1 0.370203015 0.42480123 3.27E−13 1.3155E−145 0.370203015 NA Ctsb 0.521310448 0.55397449 4.83E−13 4.5123E−149 0.521310448 NA Mug2 0.370406564 0.53657702 6.96E−26 3.3989E−113 0.368295871 0.370406564 Slc25a47 0.502661475 0.63592878  1.45E−158 0 0.428932953 NA Atf6 0.377819844 0.28052116 7.66E−12 1.54665E−82  0.377819844 NA Ell2 0.417241283 0.37174598 2.55E−22  9.305E−113 0.417241283 0.288090516 Brd2 0.571515166 0.25844685 2.65E−12 8.83728E−51  0.571515166 0.266388486 Snx10 0.285642594 0.55824463 2.35E−11 1.5948E−251 0.285642594 NA Steap4 0.475973731 1.89001517 6.59E−69 0 0.437231109 0.475973731 Gfra1 0.386382804 0.47469443 2.65E−92  4.734E−168 0.386382804 NA Cp 0.436243259 0.65551115  6.52E−192 5.8053E−290 0.254076812 0.317404056 Slc25a51 0.263985158 0.37215766 6.14E−10 1.1132E−164 0.263985158 NA Eef1a1 0.439251983 0.34076819  2.2E−81 6.1414E−119 0.282586942 0.439251983 Ivns1abp 0.356610399 0.46254094  1.2E−09 9.4406E−168 0.356610399 NA Por 0.335963246 0.29074557 1.06E−73 3.92838E−83  0.335963246 0.271635533 Plin5 0.352087102 0.48925753  1.22E−125 1.0072E−205 0.296281512 0.277759837 Ppip5k2 0.320939415 0.30299148 7.41E−09 3.6258E−115 0.320939415 NA Fmo5 0.286219883 0.6901608 4.71E−64 0 0.286219883 NA Ccnl1 0.256623048 0.34133845 1.44E−08 1.6662E−120 0.256623048 NA Nrp1 0.360791537 0.26879679 1.93E−28 7.49426E−79  0.360791537 0.334097753 H2-D1 0.286522764 0.43318371 2.31E−08 1.1359E−105 0.286522764 NA Cxcl1 0.449766784 1.23039802 9.38E−68 0 0.370070418 0.449766784 Hdlbp 0.565147241 0.39403065  5.1E−95 2.52472E−71  0.345721467 0.565147241 Hspa5 0.610549064 0.33976913  9.07E−184 1.02395E−98  0.268221373 0.610549064 Atp1a1 0.419079339 0.26171891 3.57E−63 2.95645E−65  0.419079339 0.270031448 Nucks1 0.355785584 1 2.82E−07       0.271055696 0.355785584 NA Ctnnd1 0.251848095 0.25284616 5.48E−07 1.41477E−35  0.251848095 NA Sult1a1 0.560453494 0.37102354  9.07E−216 2.6725E−99  0.318989978 NA H6pd 0.343718187 0.49196579 2.22E−16 1.0068E−111 0.343718187 0.261357904 Serinc3 0.35928911 0.29396497 4.67E−75 2.70765E−85  0.35928911 NA Il6st 0.333486533 0.38288189 3.02E−29 3.02061E−73  0.316786986 0.333486533 Elovl5 0.335236661 0.38226719      0.00000254 1.0806E−102 0.335236661 NA Cyp3a13 0.284411943 0.42068008      0.00000493 6.40777E−81  0.284411943 NA Rmnd5a 0.318903459 0.27347302      0.0000109 5.48218E−73  0.318903459 NA mmu-mir-6236 0.787474192 1.25724839 7.24E−35  5.137E−284 0.520569164 0.787474192 Saa2 0.964488054 4.43818759 8.96E−95 0 0.558658405 0.964488054 Cpt1a 0.372935212 0.42860734 2.13E−98 3.3126E−139 0.261119591 NA Acsl4 0.314743242 0.27327587 1.14E−25 5.43114E−70  0.298529302 0.314743242 Trib1 0.331693479 0.58175428 7.49E−21 1.5671E−204 0.331693479 0.287458438 Psap 0.360973931 0.31847224      0.25780026 5.29626E−54  0.257800256 NA Apcs 0.75840106 2.04948541 2.16E−78 0 0.298925674 0.606730845 Gm23935 1 1.20724431  3.7E−142 1.3842E−297 0.424222263 0.721300311 Sephs2 0.889992859 0.618707  2.83E−263 1.0636E−281 NA 0.889992859 Fgl1 0.864933885 1.56188077  1.6E−238 0 NA 0.864933885 Hyou1 0.846484822 0.49615608  1.62E−156 3.5998E−141 NA 0.846484822 Calr 0.555145472 0.39195553  1.67E−148 1.6119E−116 NA 0.555145472 Scd1 0.726687286 1.081677  2.08E−139 0 0.466125013 0.726687286 Itih4 0.525074867 1.18011817  4.26E−137 0 NA 0.525074867 Hp 0.431328341 1.5848899  8.95E−137 0 NA 0.431328341 Pdia3 0.593769188 0.27615686  7.36E−136 3.3607E−53  NA 0.593769188 P4hb 0.405223744 0.38506968  2.27E−113  1.31E−132 NA 0.405223744 Glud1 0.451048591 0.35909971  6.55E−110 1.1097E−139 NA 0.451048591 Pzp 0.41600896 0.63685181 3.34E−97 0 NA 0.41600896  Serpina10 0.565046404 0.87104418 8.21E−94 0 NA 0.565046404 Creld2 0.608652695 0.36247761 1.18E−91 5.90495E−44  NA 0.608652695 Egfr 0.504957782 0.65440823 1.72E−79 5.4692E−228 NA 0.504957782 Orm1 0.365144434 1.82376077 4.87E−78 0 NA 0.365144434 Kng1 0.265777676 0.54683549 1.32E−71 0 NA 0.265777676 Elovl2 0.45224665 0.28503861 1.22E−62 2.60256E−69  NA 0.45224665  Cps1 0.32450205 0.33642945 1.45E−55 1.1876E−145 NA 0.32450205  Prg4 0.430643187 0.81083567  3.2E−54 8.3602E−244 NA 0.430643187 Manf 0.468881688 0.28295063  1.6E−53       0.023268676 NA 0.468881688 Orm2 0.271460545 2.40508674 2.71E−53 0 NA 0.271460545 Cfh 0.400919606 0.83288399 3.24E−52 0 NA 0.400919606 Hc 0.367935082 0.61123296 1.11E−51 2.3088E−207 NA 0.367935082 Dhcr24 0.423756767 0.75973058  3.03E−107 1.4499E−130 NA 0.423756767 Cpb2 0.322179327 0.4037904 5.47E−45 3.3355E−100 0.321495225 0.322179327 Plg 0.261736006 0.5965244 1.34E−44 0 NA 0.261736006 Acox1 0.275171428 0.54002216 1.78E−40 0 NA 0.275171428 Dnajc12 0.322094554 0.31290759 1.14E−39 2.5383E−30  NA 0.322094554 C8a 0.333650228 0.40419805 7.61E−55 2.99834E−96  NA 0.333650228 Qsox1 0.342352868 0.72506211  9.2E−39 2.2371E−241 NA 0.342352868 Slc3a1 0.340997565 0.38179133  7.1E−38 1.93288E−94  NA 0.340997565 Fos 0.432003299 0.52473333 1.43E−36  3.547E−125 NA 0.432003299 Dstn 0.324301394 0.27138172 1.75E−35 2.89799E−82  NA 0.324301394 Cyb5r3 0.339033056 0.33768468  3.1E−34 1.89897E−92  NA 0.339033056 Efna1 0.336097237 0.26845518 1.73E−31 2.54995E−60  NA 0.336097237 Slc7a2 0.352564931 0.62232653 3.47E−68 6.7383E−265 NA 0.352564931 BC025446 0.29422883 0.26691138 4.26E−85 4.45527E−39  NA 0.29422883  Nedd4 0.377388355 0.2599787 6.69E−31 7.3475E−56  0.281232817 0.377388355 Lrp1 0.505128824 0.91404697 6.85E−30 2.1691E−231 NA 0.505128824 Cfi 0.251606433 0.39083407  7.2E−30 2.1633E−113 NA 0.251606433 Cmah 0.361552447 0.25131977 5.19E−29 6.55013E−28  NA 0.361552447 Mlec 0.324558531 0.4003213 7.94E−29 1.46083E−15  NA 0.324558531 Copa 0.345094339 0.29425625 1.16E−25 1.69118E−64  NA 0.345094339 Mtus1 0.362060296 0.38548314 7.17E−25 2.92023E−54  NA 0.362060296 Mtss1 0.287581972 0.55213798 1.08E−21 2.0749E−204 NA 0.287581972 Edem1 0.286881059 0.30121248 1.13E−21 1.82231E−44  NA 0.286881059 Acly 0.328803101 0.28766387 1.74E−21 4.67378E−64  NA 0.328803101 Ptprf 0.307126385 0.27768605  6.5E−20 4.49155E−33  NA 0.307126385 Osbpl9 0.278773264 0.27071381 1.04E−19 1.06115E−31  NA 0.278773264 Azin1 0.270139699 0.26889117 6.16E−19 7.98936E−76  NA 0.270139699 Iqgap2 0.254698841 0.28319294 9.72E−19 5.91083E−69  NA 0.254698841 Prox1 0.266329524 0.31520499 7.66E−14 3.0276E−77  NA 0.266329524 Caprin1 0.262825966 0.30302085 1.56E−12 2.84105E−37  NA 0.262825966 Fasn 0.291406736 0.46716808 1.44E−09 2.5454E−152 NA 0.291406736 Apoc2 0.782126085 0.51714297  3.07E−267 6.48459E−35  NA NA Ahsg 0.292489576 0.32482682  1.68E−221 3.2651E−222 NA NA Hrg 0.518895355 0.58732025  3.81E−221 3.9739E−209 NA NA Agt 0.520454244 0.25820587  1.09E−213 4.95463E−49  NA NA Igfbp4 0.43528879 0.41117468  1.54E−189 6.6901E−171 NA NA Hspa8 0.420379148 0.30215243  1.8E−143 4.30569E−21  NA 0.359978165 Serping1 0.41280952 0.53583075  1.56E−134 3.5363E−179 NA NA Rgs16 0.322559157 0.43810549  5.95E−128 3.5457E−188 NA NA Vtn 0.333811366 0.51693553  2.9E−126 8.9644E−294 NA NA Gm2a 0.383109253 0.34114593  1.13E−105 6.60916E−93  NA NA Uroc1 0.416226092 0.45932293  3.97E−100 1.13457E−82  NA NA Snord13 0.261078586 0.40878863 2.42E−99       0.000327047 NA NA Akr1d1 0.361037667 0.25829319 2.99E−98      0.00030931 0.278865899 NA Mgll 0.333899751 0.32184017 5.21E−98  6.615E−101 NA NA Fah 0.302494707 0.3255185 1.16E−92 1.50517E−71  0.259255187 NA Mttp 0.311504107 0.29665141 1.44E−86 2.14293E−79  NA NA Eci2 0.311004843 0.28815951 1.53E−86 5.23022E−88  NA NA Igf1 0.295791825 0.27713876 1.83E−78 2.85872E−86  NA NA C4b 0.283273876 0.82002299 3.16E−70 0 NA NA F9 0.256805166 0.30398094 8.09E−65 1.74064E−49  NA NA Sardh 0.269183147 0.28626336 1.48E−63 2.96273E−45  NA NA F5 0.300566587 0.43670918 3.21E−60 1.06285E−75  NA NA Lpin1 0.277494868 1.32765763 1.78E−42 0 NA NA Glul 0.379494728 1      0.00256055 1.0077E−186 NA NA ID A48A96logFC A6p A24p A48A96p PH3logFC PH48logFC Mt2 NA  1.9E−237 NA NA 2.6060431  1.558205591 Mt1 0.3563268  3.51E−232 3.61E−18  1.2E−56 2.610854994 1.733946488 Plin2 NA  8.58E−163 NA NA 0.720463076 NA Il1r1 NA  1.47E−162 NA NA 0.998168131 0.299449962 Actb 0.29414   6.06E−159 5.37E−69 8.47E−52 0.456981443 0.399035393 Cdkn1a NA  2.99E−152 NA NA 0.449325471 NA Klf6 NA  1.5E−147 NA NA 0.3616937  NA Txnrd1 NA  1.43E−144 1.44E−15 NA 0.314979852 0.252234489 Gm26924 NA  3.7E−144 0 NA 1.063463323 1.445355764 2010003K11Rik NA  2.61E−131 NA NA 0.372219971 NA Krt18 NA  3.97E−121 NA NA NA 0.520354076 Fga NA  2.44E−115 0 NA 0.981249724 0.968748472 Mat1a 1.0004332  3.26E−113 NA 0 0.623734998 0.378728792 n-R5-8s1 NA  1.81E−109 0 NA 1.289598504 1.223121237 Lars2 NA  9.69E−109  1.38E−293 NA 0.816795688 0.849538102 Myh9 NA  3.1E−107 2.47E−87 NA 0.399128031 0.438269269 Fgg NA  1.29E−106 0 NA 0.809322713 0.702140119 Gm24601 NA  4.45E−106  2.17E−275 NA 0.924568273 0.675379727 Fgb NA  4.4E−105 0 NA 0.739519125 0.677592366 Gm15564 NA  4.17E−104  6.31E−292 NA 0.735157137 0.746211054 Krt8 NA  1.04E−103 NA NA NA 0.252276759 Clec4f NA  2.17E−103 NA NA NA 0.380337956 Apoa4 0.4955793  8.56E−101 NA 8.65E−87 0.609214916 1.186863065 Bcl2l1 NA 1.02E−99 NA NA 0.280315334 NA Serpina3m 0.4325834  2.5E−94 NA  1.04E−130 0.779052745 0.519751144 Rcan1 NA 1.24E−93 NA NA 0.509239866 NA D10Wsu102e NA 2.09E−90 NA NA 0.256022156 NA Slc39a14 NA 2.25E−81 8.94E−22 NA 0.831584936 NA C1qb NA 1.02E−79 NA NA NA 0.361309767 Tmsb4x NA 7.99E−79 NA NA NA 0.347657914 Ctss NA 2.26E−78 NA NA NA NA Mrap NA 2.65E−73 NA NA NA 0.280974611 Hnf4a 0.3147106 6.36E−71 9.91E−71 3.56E−83 0.644195253 NA Csf1r NA  4.7E−70 NA NA NA 0.284684372 Trp53inp1 NA 1.52E−67 2.95E−29 NA 0.269278401 NA Nop58 NA 2.13E−65 NA NA 0.257566653 NA Mfsd2a 0.6122327 7.88E−65 NA  5.34E−233 0.496351884 NA Lyz2 NA 2.49E−63 NA NA NA 0.275390862 Bach1 NA 2.51E−63 NA NA 0.533237374 NA Fam134b NA 5.02E−63 NA NA 0.865578177 NA Cd5l NA 1.08E−62 NA NA NA 0.460825248 Serpina3n 0.3464828 4.98E−61 4.35E−45 9.93E−85 1.759758939 1.082720183 Apob NA 5.69E−61 4.36E−68 NA 0.416824707 NA Eif1a NA  1.8E−60 NA NA 0.295219945 NA Epas1 NA 7.57E−60 NA NA 0.38425941  NA Sdc4 NA 9.47E−59 NA NA 0.43560504  NA C3 0.2591667 1.55E−58  1.23E−125  1.44E−100 0.482674202 0.982337034 Wfdc17 NA 2.57E−58 NA NA NA NA Fkbp5 NA 1.44E−57 NA NA 0.663304836 NA Btg2 NA 3.81E−56 NA NA 0.772686832 0.280923811 Tiparp NA 8.73E−55 NA NA 0.489122153 NA Cldn14 NA 1.86E−52 NA NA 0.511583526 NA Abhd2 NA 1.13E−50 NA NA NA NA Picalm NA 1.39E−50 NA NA 0.276902165 NA Igfbp1 NA 1.68E−50 9.05E−32 NA 1.288789902 0.466237818 Stat3 NA 2.74E−50 8.01E−18 NA 0.460515229 0.308012615 Myo1e NA 9.34E−50 NA NA 0.399456672 NA Tmem87b NA 1.07E−49 NA NA 0.288330587 NA Slc10a2 NA 2.04E−49 NA NA 0.30563824  NA Lcn2 NA 2.72E−49 NA NA 1.499141183 2.39758181  Jmjd1c NA 3.43E−49 NA NA 0.39612601  NA Itih3 NA  1.4E−47 1.11E−89 NA 0.469631651 1.223022315 Tacc2 NA 3.95E−42 NA NA 0.877623973 NA Eef2 NA 2.71E−41 2.54E−28 NA 0.289562847 NA Ptpn1 NA 3.51E−41 NA NA 0.268263225 NA Tnfrsf1a NA 3.86E−41 NA NA 0.346845029 NA Ddx3x NA 1.07E−40 NA NA 0.47100162  NA Itih2 NA 3.43E−38 6.17E−35 NA 0.336714211 0.312933325 St3gal5 0.5423784 6.13E−38 NA  1.06E−170 0.882761517 NA Abca1 NA 8.81E−38 4.14E−37 NA 0.50506234  NA Bcl3 NA 3.63E−37 NA NA 0.419650143 NA Asl 0.4384583 8.13E−37 NA  3.45E−117 0.297673772 NA Aldob 0.3654606 1.58E−35 NA  9.03E−178 0.490200848 0.254127817 Ugdh NA 5.17E−34 NA NA NA 0.260443532 H3f3b NA 7.03E−34 NA NA 0.755567107 NA Xbp1 NA 9.59E−34 NA NA 0.539986   NA Ctsl NA 1.93E−33 NA NA 0.256520866 NA Hspb8 NA   2E−33 NA NA 0.667847253 NA Eif4g2 NA 5.94E−33 1.62E−67 NA 0.384302798 NA Epb4.1 NA 1.67E−30 NA NA 0.349430673 NA Rnd3 NA 3.93E−30 NA NA 0.285147682 NA Ddx5 NA  5.9E−30 NA NA 0.251675045 NA Plec NA  8.3E−30 NA NA NA NA Jak1 NA 1.34E−29  1.2E−17 NA 0.362766687 NA Errfi1 NA 1.52E−29 NA NA 0.500850526 NA Iigp1 NA 2.65E−29 7.59E−66 NA NA NA Lrg1 NA 1.92E−28 1.37E−62 NA 0.870250525 1.051046086 Gpt2 NA 2.49E−28 NA NA 0.533331785 NA Gjb2 NA 1.12E−27 3.74E−38 NA 0.639507436 0.328679811 Dst NA 2.08E−26 1.75E−35 NA 0.329905553 NA Wbp1l 0.4404629 2.48E−26 NA  4.08E−134 0.409138156 NA Fn1 0.2925222 2.99E−26  1.87E−106 3.08E−64 0.684266092 0.469732274 Grn 0.4732523 1.38E−25 NA  1.07E−154 0.403315761 0.293077345 Mpeg1 NA  1.8E−24 NA NA NA NA Aff4 NA 1.96E−24 NA NA 0.344186222 NA Gm26917 NA  6.5E−24 5.26E−54 NA 0.46739621  0.475554164 Tns1 NA  8.9E−24 NA NA 0.33981795  NA Arg1 NA 8.62E−23 NA NA 0.381616351 NA Arhgef12 NA 8.83E−23 1.41E−20 NA 0.280147378 NA Man2a1 0.3327558 6.13E−22 2.79E−19 2.32E−81 0.369999358 NA Lpgat1 0.2576004 4.45E−21 3.86E−28 3.53E−63 0.390146943 0.347767347 Il6ra NA 5.08E−20 NA NA 0.251696836 NA Ptp4a1 NA 3.82E−19 NA NA 0.393137367 NA Atp2a2 0.3056362  2.9E−18 NA 7.58E−69 0.350363266 NA Aass NA 3.07E−18 NA NA 0.705615345 NA Nedd4l NA  4.9E−18 NA NA 0.271827098 NA Egr1 NA  2.8E−17 NA NA 0.620480469 NA Litaf NA 2.04E−16 NA NA 0.396007707 NA Plk3 NA 3.12E−16 NA NA 0.488016367 NA Slc41a2 NA 6.42E−16 2.13E−34 NA 0.3685439  0.318516467 Hsp90ab1 NA 8.34E−16 NA NA NA 0.455851506 Tgm2 NA 1.43E−15 NA NA 0.316575272 0.37123494  Shb NA 4.68E−15 NA NA 0.430613558 NA Tmed5 0.3450078 1.17E−13 NA  5.01E−102 0.296018777 NA Atp1b1 NA 3.27E−13 NA NA 0.424801231 NA Ctsb NA 4.83E−13 NA NA 0.268200419 0.310468937 Mug2 NA 9.47E−13 6.96E−26 NA NA NA Slc25a47 0.5026615 2.18E−12 NA  1.45E−158 0.635928777 0.555532536 Atf6 NA 7.66E−12 NA NA 0.280521162 NA Ell2 NA 8.49E−12 2.55E−22 NA 0.371745977 NA Brd2 NA 1.73E−11 2.65E−12 NA 0.258446853 NA Snx10 NA 2.35E−11 NA NA 0.558244633 0.253822304 Steap4 NA 3.54E−11 6.59E−69 NA 1.890015167 0.631013696 Gfra1 0.3208433 8.44E−11 NA 2.65E−92 0.474694426 NA Cp 0.4362433 2.41E−10 1.74E−45  6.52E−192 NA 0.620221202 Slc25a51 NA 6.14E−10 NA NA 0.372157664 NA Eef1a1 NA 1.02E−09  2.2E−81 NA 0.340768186 0.254969818 Ivns1abp NA  1.2E−09 NA NA 0.46254094  NA Por 0.3319492 4.49E−09 2.42E−08 1.06E−73 0.290745567 NA Plin5 0.3520871 6.88E−09 2.38E−16  1.22E−125 0.489257529 NA Ppip5k2 NA 7.41E−09 NA NA 0.30299148  NA Fmo5 0.2520709 1.05E−08 NA 4.71E−64 0.690160801 0.379271143 Ccnl1 NA 1.44E−08 NA NA 0.341338448 NA Nrp1 NA 2.25E−08 1.93E−28 NA 0.268796793 NA H2-D1 NA 2.31E−08 NA NA NA NA Cxcl1 0.2572501 4.89E−08 1.26E−30 9.38E−68 1.230398019 0.353012683 Hdlbp NA 0.000000054  5.1E−95 NA 0.267317937 NA Hspa5 0.2911841 9.35E−08  9.07E−184 2.27E−84 NA 0.270882455 Atp1a1 0.2627704 0.000000242      0.00000197 3.57E−63 0.261718912 NA Nucks1 NA 0.000000282 NA NA NA 0.271055696 Ctnnd1 NA 0.000000548 NA NA NA NA Sult1a1 0.5604535 0.000000664 NA  9.07E−216 0.371023537 0.344836675 H6pd NA 0.000000926 2.22E−16 NA 0.300492669 NA Serinc3 0.2923207 0.00000117  NA 4.67E−75 0.293964974 NA Il6st NA 0.00000169  3.02E−29 NA 0.262348153 NA Elovl5 NA 0.00000254  NA NA 0.382267188 NA Cyp3a13 NA 0.00000493  NA NA NA NA Rmnd5a NA 0.0000109  NA NA 0.273473023 NA mmu-mir-6236 0.429737  0.0000218  7.24E−35   2E−10 0.468866739 0.632369146 Saa2 0.390082  0.000262015 8.96E−95 6.06E−64 2.971862499 4.43818759  Cpt1a 0.3729352 0.000289401 NA 2.13E−98 0.42860734  NA Acsl4 NA 0.000351815 1.14E−25 NA 0.250793464 0.273275871 Trib1 NA 0.001450331 7.49E−21 NA 0.581754281 NA Psap NA 0.360973931 NA NA NA NA Apcs NA 0.75840106  2.16E−78 NA 0.573439593 2.049485412 Gm23935 0.5019442 1             0.068577969  3.7E−142 0.498066925 0.562414557 Sephs2 NA NA  2.83E−263 NA 0.618707003 NA Fgl1 NA NA  1.6E−238 NA 0.49338252  1.561880768 Hyou1 NA NA  1.62E−156 NA 0.431109873 0.315760783 Calr NA NA  1.67E−148 NA NA NA Scd1 0.5192181 5.04E−19  2.08E−139  5.06E−126 1.081676999 NA Itih4 NA NA  4.26E−137 NA 0.887186241 1.171742648 Hp NA NA  8.95E−137 NA 0.774785279 1.584889895 Pdia3 NA NA  7.36E−136 NA NA NA P4hb 0.2506609 NA  2.27E−113 1.25E−84 NA 0.38506968  Glud1 NA NA  6.55E−110 NA 0.341724783 0.359099708 Pzp NA NA 3.34E−97 NA 0.387351113 0.382796555 Serpina10 NA NA 8.21E−94 NA 0.733655099 0.871044179 Creld2 NA NA 1.18E−91 NA NA 0.362477611 Egfr 0.473389  NA 1.72E−79 5.82E−71 0.555834247 NA Orm1 0.310039  NA 4.87E−78 1.56E−69 0.463411533 1.823760769 Kng1 NA NA 1.32E−71 NA NA 0.419944891 Elovl2 NA NA 1.22E−62 NA 0.285038606 NA Cps1 NA NA 1.45E−55 NA 0.336429448 NA Prg4 NA NA  3.2E−54 NA 0.480504574 0.355545985 Manf NA NA  1.6E−53 NA NA 0.282950631 Orm2 NA NA 2.71E−53 NA NA 2.405086745 Cfh 0.306326  NA 3.24E−52 2.09E−34 0.312615767 0.588715272 Hc NA NA 1.11E−51 NA NA NA Dhcr24 0.3872743 NA 3.44E−48  3.03E−107 NA 0.759730578 Cpb2 NA 4.76E−14 5.47E−45 NA 0.280302458 0.395699062 Plg NA NA 1.34E−44 NA 0.26619661  NA Acox1 NA NA 1.78E−40 NA 0.540022158 NA Dnajc12 NA NA 1.14E−39 NA NA 0.312907586 C8a 0.327131  NA 3.84E−39 7.61E−55 0.294064237 NA Qsox1 NA NA  9.2E−39 NA 0.378486857 0.551776463 Slc3a1 NA NA  7.1E−38 NA 0.290117272 0.321802388 Fos NA NA 1.43E−36 NA 0.524733327 NA Dstn NA NA 1.75E−35 NA 0.271381717 NA Cyb5r3 NA NA  3.1E−34 NA 0.337684684 NA Efna1 NA NA 1.73E−31 NA 0.256152989 NA Slc7a2 0.3449781 NA 1.75E−31 3.47E−68 0.622326529 NA BC025446 0.2726109 NA 6.33E−31 4.26E−85 NA NA Nedd4 NA  4.9E−18 6.69E−31 NA 0.259978699 NA Lrp1 NA NA 6.85E−30 NA 0.310226628 0.314138344 Cfi NA NA  7.2E−30 NA NA NA Cmah NA NA 5.19E−29 NA NA NA Mlec NA NA 7.94E−29 NA NA 0.400321297 Copa NA NA 1.16E−25 NA 0.251410027 NA Mtus1 NA NA 7.17E−25 NA 0.268076242 NA Mtss1 NA NA 1.08E−21 NA 0.552137981 NA Edem1 NA NA 1.13E−21 NA NA NA Acly NA NA 1.74E−21 NA 0.287663867 NA Ptprf NA NA  6.5E−20 NA NA NA Osbpl9 NA NA 1.04E−19 NA NA NA Azin1 NA NA 6.16E−19 NA 0.268891169 NA Iqgap2 NA NA 9.72E−19 NA 0.283192936 NA Prox1 NA NA 7.66E−14 NA 0.31520499  NA Caprin1 NA NA 1.56E−12 NA NA 0.303020851 Fasn NA NA 1.44E−09 NA 0.467168076 NA Apoc2 0.7821261 NA NA  3.07E−267 NA 0.517142972 Ahsg 0.2924896 NA NA  1.68E−221 NA 0.281450293 Hrg 0.5188954 NA NA  3.81E−221 NA 0.270451116 Agt 0.5204542 NA NA  1.09E−213 NA NA Igfbp4 0.4352888 NA NA  1.54E−189 0.387861679 NA Hspa8 0.4203791 NA 1.12E−41  1.8E−143 NA 0.302152434 Serping1 0.4128095 NA NA  1.56E−134 NA NA Rgs16 0.3225592 NA NA  5.95E−128 0.438105488 NA Vtn 0.3338114 NA NA  2.9E−126 NA NA Gm2a 0.3831093 NA NA  1.13E−105 0.341145926 NA Uroc1 0.4162261 NA NA  3.97E−100 0.329587334 NA Snord13 0.2610786 NA NA 2.42E−99 NA 0.408788625 Akr1d1 0.3610377 6.11E−10 NA 2.99E−98 NA 0.258293189 Mgll 0.3338998 NA NA 5.21E−98 0.321840174 NA Fah 0.3024947 1.82E−10 NA 1.16E−92 NA NA Mttp 0.3115041 NA NA 1.44E−86 0.296651415 NA Eci2 0.3110048 NA NA 1.53E−86 0.288159513 NA Igf1 0.2957918 NA NA 1.83E−78 0.277138761 NA C4b 0.2832739 NA NA 3.16E−70 0.26668764  0.530516995 F9 0.2568052 NA NA 8.09E−65 NA NA Sardh 0.2691831 NA NA 1.48E−63 NA NA F5 0.3005666 NA NA 3.21E−60 NA NA Lpin1 0.2774949 NA NA 1.78E−42 1.327657625 NA Glul 0.3794947 NA NA      0.00256055 0.478908893 0.611936929 ID PH120logFC PH3p PH48p PH120p Mt2 1.471840722 0  2.0362E−271 0 Mt1 1.65972779  0  9.8777E−293 0 Plin2 NA 0 NA NA Il1r1 0.63980318  0 2.79338E−18  4.6854E−177 Actb NA 2.1478E−210 2.62127E−44 NA Cdkn1a NA  7.064E−169 NA NA Klf6 NA 8.0005E−203 NA NA Txnrd1 NA 3.22341E−84        0.032529357 NA Gm26924 1.379756734 0 0 0 2010003K11Rik NA 1.0574E−239 NA NA Krt18 NA NA 5.88314E−34 NA Fga 1.039432587 0  9.2714E−246 0 Mat1a 0.519634823 0 5.65122E−41   2.896E−246 n-R5-8s1 1.066654791 0  2.9367E−283 0 Lars2 1.419129056 0  4.7257E−222 0 Myh9 0.631035657 3.0354E−126 1.59002E−15  2.8315E−141 Fgg 0.686743278 0  3.4215E−167 0 Gm24601 0.675086715 0  2.6798E−176 0 Fgb 0.605783409 0  1.4129E−179 0 Gm15564 1.485885928 0  4.3231E−146 0 Krt8 NA NA       0.182829207 NA Clec4f 0.487336922 NA 1.17731E−53  1.7326E−119 Apoa4 NA 2.34147E−92   3.0126E−137 NA Bcl2l1 NA 1.1685E−128 NA NA Serpina3m 0.305171041 0  1.275E−57 2.79622E−48 Rcan1 NA 4.5798E−279 NA NA D10Wsu102e NA 1.0336E−141 NA NA Slc39a14 0.506662289 0 NA  1.1603E−108 C1qb 0.337494489 NA  2.5047E−59  6.3479E−100 Tmsb4x 0.341035762 NA 7.53442E−31 1.30373E−70 Ctss 0.270183132 NA NA 2.67839E−57 Mrap NA NA 1.03675E−10 NA Hnf4a 0.470873585 5.6829E−290 NA  3.0788E−110 Csf1r NA NA 3.78986E−37 NA Trp53inp1 NA 1.01347E−72  NA NA Nop58 NA 1.11973E−93  NA NA Mfsd2a NA 1.6404E−219 NA NA Lyz2 0.402735723 NA 1.20955E−28 3.32908E−93 Bach1 NA 5.5373E−247 NA NA Fam134b NA 0 NA NA Cd5l 0.49371428  NA  2.074E−79  4.6843E−138 Serpina3n 1.205364333 0  4.6706E−169 0 Apob 0.505397578  8.048E−169 NA  4.6275E−151 Eif1a NA 7.80345E−96  NA NA Epas1 NA 2.1215E−138 NA NA Sdc4 0.315436107 2.7024E−193 NA 2.09944E−74 C3 1.071950932 0 0 0 Wfdc17 0.317329894 NA NA  1.3239E−101 Fkbp5 NA 0 NA NA Btg2 0.386164963 7.2437E−290 2.37272E−05 2.69258E−68 Tiparp NA 7.0657E−236 NA NA Cldn14 NA  4.316E−281 NA NA Abhd2 0.267241512 NA NA 1.29723E−66 Picalm NA 1.27269E−76  NA NA Igfbp1 0.488899754 0 2.67298E−25 1.15024E−78 Stat3 0.483904634 3.5753E−174 2.82354E−05  1.7545E−98 Myo1e NA 7.8258E−162 NA NA Tmem87b NA 8.7183E−155 NA NA Slc10a2 NA  6.538E−197 NA NA Lcn2 2.127649068 0 0 0 Jmjd1c NA 1.0512E−144 NA NA Itih3 1.177912468 1.1211E−197  4.0411E−297 0 Tacc2 NA 0 NA NA Eef2 0.321705764 1.70104E−97  NA 1.01772E−72 Ptpn1 NA 6.9212E−130 NA NA Tnfrsf1a 0.267537895 3.4204E−112 NA 1.90007E−43 Ddx3x NA 1.3581E−155 NA NA Itih2 NA 1.5587E−122 2.29359E−24 NA St3gal5 NA 0 NA NA Abca1 0.370856836 3.1915E−172 NA 2.16402E−52 Bcl3 NA 3.0494E−251 NA NA Asl NA 1.76334E−83  NA NA Aldob NA 0 2.24769E−64 NA Ugdh NA NA 4.68355E−05 NA H3f3b NA 4.4441E−288 NA NA Xbp1 NA 1.3385E−208 NA NA Ctsl NA 1.56147E−59  NA NA Hspb8 0.52383406  9.1859E−267 NA  4.2261E−133 Eif4g2 0.287105046  2.505E−110 NA 8.06734E−39 Epb4.1 NA 1.9295E−113 NA NA Rnd3 NA 4.6581E−134 NA NA Ddx5 NA 3.02351E−75  NA NA Plec 0.267122123 NA NA 2.03726E−37 Jak1 NA 2.4382E−103 NA NA Errfi1 NA 7.4336E−262 NA NA Iigp1 0.305889089 NA NA 4.94888E−49 Lrg1 1.260509735 0  1.5393E−213 0 Gpt2 NA 3.6697E−218 NA NA Gjb2 0.402811227 9.9227E−255 2.44199E−12 1.87917E−70 Dst NA 7.3975E−105 NA NA Wbp1l NA 1.2925E−127 NA NA Fn1 1.018772906 5.5621E−298 5.12048E−32 0 Grn 0.316049742 3.4391E−128 4.46789E−10 1.12476E−47 Mpeg1 0.541170007 NA NA  4.2393E−174 Aff4 NA 7.00106E−97  NA NA Gm26917 0.443747552 2.4164E−144 2.51697E−05 7.15171E−51 Tns1 NA 4.5763E−128 NA NA Arg1 NA  2.227E−218 NA NA Arhgef12 0.304865834 1.49183E−67  NA 1.25661E−32 Man2a1 0.323273082 3.60298E−98  NA 1.18903E−46 Lpgat1 0.400787984 1.2472E−107 1.05076E−09 1.04662E−64 Il6ra NA 2.9323E−108 NA NA Ptp4a1 NA 6.0997E−190 NA NA Atp2a2 0.263222967 8.21385E−94  NA  4.4193E−29 Aass 0.312355615 1.0663E−286 NA 3.70382E−47 Nedd4l NA 1.5124E−116 NA NA Egr1 0.271667356 7.2676E−185 NA 3.36174E−20 Litaf NA  2.337E−132 NA NA Plk3 NA 8.2222E−205 NA NA Slc41a2 0.441321771 2.2246E−166 5.59542E−25  4.3631E−127 Hsp90ab1 0.323037124 NA 1.23192E−83 1.16529E−94 Tgm2 0.342526865 5.49556E−85  5.93696E−16 2.52488E−59 Shb NA 4.0274E−182 NA NA Tmed5 NA 1.362E−80 NA NA Atp1b1 NA 1.3155E−145 NA NA Ctsb 0.553974491 1.08822E−72   2.1673E−12  4.5123E−149 Mug2 0.536577024 NA NA  3.3989E−113 Slc25a47 NA 0  2.8075E−104 NA Atf6 NA 1.54665E−82  NA NA Ell2 NA  9.305E−113 NA NA Brd2 NA 8.83728E−51  NA NA Snx10 NA 1.5948E−251 1.27886E−13 NA Steap4 0.931387724 0 4.71389E−63  1.3111E−284 Gfra1 NA  4.734E−168 NA NA Cp 0.655511152 NA   1.411E−115  5.8053E−290 Slc25a51 NA 1.1132E−164 NA NA Eef1a1 NA 6.1414E−119 1.24947E−12 NA Ivns1abp NA 9.4406E−168 NA NA Por NA 3.92838E−83  NA NA Plin5 NA 1.0072E−205 NA NA Ppip5k2 NA 3.6258E−115 NA NA Fmo5 0.337493236 0 1.75071E−43 5.95154E−73 Ccnl1 NA 1.6662E−120 NA NA Nrp1 NA 7.49426E−79  NA NA H2-D1 0.433183706 NA NA  1.1359E−105 Cxcl1 NA 0 7.28481E−05 NA Hdlbp 0.394030651 3.33056E−59  NA 2.52472E−71 Hspa5 0.339769129 NA 2.26522E−12 1.02395E−98 Atp1a1 NA 2.95645E−65  NA NA Nucks1 NA NA 1 NA Ctnnd1 0.252846161 NA NA 1.41477E−35 Sult1a1 NA 2.6725E−99  2.16219E−12 NA H6pd 0.491965789 1.9138E−81  NA  1.0068E−111 Serinc3 NA 2.70765E−85  NA NA Il6st 0.382881893 3.02061E−73  NA 3.34974E−58 Elovl5 NA 1.0806E−102 NA NA Cyp3a13 0.420680082 NA NA 6.40777E−81 Rmnd5a NA 5.48218E−73  NA NA mmu-mir-6236 1.257248389 4.5061E−221 5.48505E−97   5.137E−284 Saa2 3.598008691 0 0 0 Cpt1a 0.276570679 3.3126E−139 NA 1.18854E−34 Acsl4 NA 5.43114E−70        0.003086449 NA Trib1 NA 1.5671E−204 NA NA Psap 0.318472244 NA NA 5.29626E−54 Apcs 0.965147497 2.0613E−182 0  5.9431E−275 Gm23935 1.207244314 8.5684E−162 2.20888E−73  1.3842E−297 Sephs2 0.604852301 1.0636E−281 NA  1.8569E−182 Fgl1 1.379926505 2.3577E−175 0 0 Hyou1 0.496156079 3.5998E−141       0.000165574 3.38682E−91 Calr 0.391955529 NA NA  1.6119E−116 Scd1 0.787835318 0 NA  3.7098E−204 Itih4 1.18011817  0 0 0 Hp 1.107075607 0 0 0 Pdia3 0.276156858 NA NA  3.3607E−53 P4hb 0.369961971 NA 1.73293E−74   1.31E−132 Glud1 0.307823999 1.1097E−139 4.69364E−47 1.29722E−69 Pzp 0.636851805 2.8474E−237 2.61472E−52 0 Serpina10 0.740578005 0  3.5999E−107  1.3451E−230 Creld2 0.307177214 NA 1.11415E−08 5.90495E−44 Egfr 0.65440823  5.4692E−228 NA  4.2603E−199 Orm1 1.05827481   4.577E−180 0 0 Kng1 0.546835494 NA  3.9248E−102 0 Elovl2 NA 2.60256E−69  NA NA Cps1 0.312297912 1.1876E−145 NA 8.38552E−77 Prg4 0.810835665 4.3499E−189 1.45301E−24  8.3602E−244 Manf NA NA       0.023268676 NA Orm2 1.536747401 NA 0 0 Cfh 0.83288399  3.4561E−113  2.5189E−103 0 Hc 0.611232959 NA NA  2.3088E−207 Dhcr24 0.551421264 NA  1.6476E−115  1.4499E−130 Cpb2 0.403790403 1.58681E−74  1.08559E−38  3.3355E−100 Plg 0.596524395 1.3469E−121 NA 0 Acox1 0.292890336 0 NA 1.80286E−68 Dnajc12 NA NA  2.5383E−30 NA C8a 0.404198047 1.39461E−84  NA 2.99834E−96 Qsox1 0.725062115 3.7529E−121  2.238E−55  2.2371E−241 Slc3a1 0.381791335 1.93288E−94  1.78412E−11 2.58695E−55 Fos NA  3.547E−125 NA NA Dstn NA 2.89799E−82  NA NA Cyb5r3 NA 1.89897E−92  NA NA Efna1 0.268455179 2.54995E−60  NA 2.85495E−25 Slc7a2 0.374380964 6.7383E−265 NA 2.68204E−62 BC025446 0.266911384 NA NA 4.45527E−39 Nedd4 NA 7.3475E−56  NA NA Lrp1 0.914046975 2.25364E−68  2.74872E−05  2.1691E−231 Cfi 0.390834066 NA NA  2.1633E−113 Cmah 0.251319774 NA NA 6.55013E−28 Mlec NA NA 1.46083E−15 NA Copa 0.294256247 1.69118E−64  NA 4.74634E−40 Mtus1 0.385483144 2.92023E−54  NA 4.22517E−49 Mtss1 0.339863924 2.0749E−204 NA 1.12341E−54 Edem1 0.301212478 NA NA 1.82231E−44 Acly NA 4.67378E−64  NA NA Ptprf 0.27768605  NA NA 4.49155E−33 Osbpl9 0.270713808 NA NA 1.06115E−31 Azin1 NA 7.98936E−76  NA NA Iqgap2 NA 5.91083E−69  NA NA Prox1 NA 3.0276E−77  NA NA Caprin1 0.295892842 NA       0.016747307 2.84105E−37 Fasn NA 2.5454E−152 NA NA Apoc2 NA NA 6.48459E−35 NA Ahsg 0.32482682  NA 7.28765E−69  3.2651E−222 Hrg 0.58732025  NA 6.86112E−14  3.9739E−209 Agt 0.258205872 NA NA 4.95463E−49 Igfbp4 0.411174683 6.6901E−171 NA  1.2719E−128 Hspa8 NA NA 4.30569E−21 NA Serping1 0.535830748 NA NA  3.5363E−179 Rgs16 NA 3.5457E−188 NA NA Vtn 0.516935534 NA NA  8.9644E−294 Gm2a NA 6.60916E−93  NA NA Uroc1 0.459322934 1.13457E−82  NA 3.99387E−76 Snord13 NA NA       0.000327047 NA Akr1d1 NA NA      0.00030931 NA Mgll NA  6.615E−101 NA NA Fah 0.325518495 NA NA 1.50517E−71 Mttp NA 2.14293E−79  NA NA Eci2 NA 5.23022E−88  NA NA Igf1 NA 2.85872E−86  NA NA C4b 0.820022988 4.29867E−67  7.45309E−90 0 F9 0.303980935 NA NA 1.74064E−49 Sardh 0.28626336  NA NA 2.96273E−45 F5 0.436709177 NA NA 1.06285E−75 Lpin1 0.382955017 0 NA 4.53406E−64 Glul 0.495360357 1.0077E−186 1       0.000261488

Albumin is the most abundant serum protein and is produced by all hepatocytes across the liver lobule, with the highest expression in the periportal region. Acute injury in both models resulted in a dramatic upregulation of albumin across the entire liver lobule beginning at the earliest observed time points (A6 and P3) (FIG. 20E). However, select genes involved in essential liver function responded at a level correlative to the extent of injury (F2 and Pck1). This is consistent with the larger total loss of hepatocytes in the PH model compared to the APAP model (˜70% vs ˜10%, respectively), resulting in a greater need for functional compensation. Applicants observed a dramatic up-regulation in metallothionein (Mt1) in both injury models (FIG. 20E). It has been suggested that Mt1 may serve two purposes in tissue injury: protection against further oxidative damage and support for the proliferative response²⁷. Further, Mt1 has previously been shown to be upregulated in the liver following PH^(28,29). Mt1 was upregulated in all hepatocytes across the lobule and to a greater degree in PH than APAP. It remained elevated throughout the PH time course, where an increased proliferative demand is present due to increased tissue loss. These findings highlight not only the rapidity of hepatic functional adaptation but also the plasticity of hepatocytes across the liver lobule.

Cell Proliferation is Inversely Correlated with Functional Adaptation

Liver regeneration research has traditionally focused on hepatocyte proliferation⁴⁻⁷. It is unknown whether actively dividing hepatocytes can equally contribute to functional compensation. Applicants observed a down-regulation of many hepatic function genes during activation of the proliferative response (A24, P48, FIG. 20E). Therefore, Applicants identified cells that became transcriptionally active for cell cycle genes in the scRNA-Seq dataset (FIG. 21A), and analyzed hepatocyte-specific transcript output compared to those cells at all time points that are not cycling. Compared to non-cycling cells (NC), there was a significant down-regulation of the Hepatocyte Signature Score in cycling cells (CC) in both injury conditions (FIG. 21B, 21C, FIG. 29 , Methods). DEG revealed substantial differences between cycling and non-cycling cells. CCs expressed many classic cell proliferation markers and exhibited down-regulation of many hepatic function genes (FIG. 21D, Table 16). Proliferating hepatocytes in general scored lower for hepatocyte markers. This was corroborated in individual cells by smFISH for the glucose transporter Slc2a2 and immunofluorescent co-staining for proliferating cell nuclear antigen (PCNA, FIG. 21E, 21F), as well as mathematical modeling of the correlation of gene expression and PCNA protein levels (FIG. 21G, Methods). Other genes, such as Alb, did not appreciably change in NC vs. CC populations (FIG. 21E-21G). Taken together, these data suggest that proliferating hepatocytes have the ability to maintain expression of select hepatic functional markers, while many other hepatic genes appear to be compensated predominantly by non-proliferating hepatocytes.

TABLE 16 DEG for each treatment between cycling cells vs noncycling cells (CC vs NC). Positive log fold-change (avg_logFC) values indicate genes up-regulated in the CCs, negative values indicate genes up-regulated in the NCs. Calculated using the FindMarkers function in the R package Seurat using the Wilcox test. ID p_val avg_logFC pct.1 pct.2 p_val_adj D17H6S56E-5 8.62E−39 1.669915133 0.747 0.057 2.14E−34 Top2a 3.79E−30 1.423669967 0.586 0.023 9.42E−26 Esco2 1.69E−28 1.063954263 0.563 0.023 4.19E−24 Cdca3 1.87E−28 1.007478565 0.598 0.04 4.64E−24 Birc5 2.19E−27 0.939238952 0.552 0.023 5.43E−23 Tubb5 1.64E−26 1.236380405 0.741 0.27 4.07E−22 Hmmr 1.68E−26 1.114822336 0.511 0.006 4.17E−22 Cdk1 6.10E−26 0.983632101 0.517 0.017 1.52E−21 Prc1 2.43E−25 0.996936039 0.494 0.006 6.04E−21 Ect2 5.32E−25 0.886912155 0.489 0.006 1.32E−20 Tubb4b 1.44E−24 1.145456059 0.753 0.322 3.56E−20 Mki67 2.01E−24 1.416251498 0.523 0.034 4.99E−20 Smc4 3.92E−23 1.307409004 0.649 0.195 9.74E−19 Rrm2 9.27E−22 0.889506091 0.5 0.046 2.30E−17 Smc2 2.33E−21 0.902524002 0.477 0.034 5.78E−17 Cdc20 3.48E−21 1.087349379 0.454 0.023 8.65E−17 Tpx2 7.77E−21 0.859308828 0.431 0.011 1.93E−16 Ckap21 8.84E−21 0.876202937 0.408 0 2.20E−16 Ckap2 1.88E−20 0.747241586 0.402 0 4.68E−16 Ccna2 1.71E−19 0.604307576 0.397 0.006 4.24E−15 Aurka 3.03E−19 0.703458561 0.391 0.006 7.51E−15 Spc25 3.03E−19 0.817339295 0.471 0.057 7.53E−15 Cenpf 8.07E−19 1.039724096 0.402 0.017 2.00E−14 Pbk 1.10E−18 0.591264838 0.385 0.006 2.72E−14 Spc24 2.45E−18 0.770336501 0.534 0.126 6.09E−14 Nek2 4.81E−18 0.722477841 0.379 0.011 1.19E−13 Knstm 1.04E−16 0.718716577 0.356 0.011 2.57E−12 Kif20b 1.19E−16 0.714194384 0.333 0 2.96E−12 Nuf2 1.19E−16 0.537828732 0.333 0 2.96E−12 Nusap1 2.41E−16 0.528310034 0.328 0 5.98E−12 Racgap1 2.58E−16 0.493496977 0.339 0.006 6.42E−12 Nucks1 3.01E−16 0.858143103 0.736 0.443 7.46E−12 Kif20a 4.27E−16 0.68044045 0.379 0.029 1.06E−11 RP23-45G16.5 5.85E−16 0.702310221 0.385 0.034 1.45E−11 Ube2c 1.66E−15 0.722670005 0.345 0.017 4.12E−11 Nudt7 3.26E−15 −0.78138871 0.552 0.793 8.11E−11 Cenpa 3.29E−15 0.567785956 0.391 0.04 8.16E−11 Ccnb2 9.67E−15 0.616222031 0.379 0.04 2.40E−10 Anln 1.14E−14 0.635712412 0.322 0.011 2.83E−10 Prim1 1.26E−14 0.631016973 0.414 0.069 3.12E−10 Rrm1 1.42E−14 0.677696452 0.391 0.052 3.52E−10 Kif11 2.77E−14 0.564607575 0.31 0.011 6.87E−10 Cdkn1a 4.16E−14 0.758583248 0.5 0.155 1.03E−09 C330027C09Rik 6.06E−14 0.591386211 0.368 0.046 1.51E−09 Tubb6 6.78E−14 0.681201202 0.408 0.075 1.68E−09 Ncapg 9.52E−14 0.473229133 0.316 0.017 2.36E−09 Tuba1b 9.63E−14 0.557598251 0.425 0.086 2.39E−09 Tacc3 9.94E−14 0.475936269 0.339 0.029 2.47E−09 Cenpq 1.16E−13 0.525048378 0.333 0.029 2.87E−09 Ezh2 1.92E−13 0.548750728 0.356 0.046 4.78E−09 Arl6ip1 1.93E−13 0.911516088 0.799 0.649 4.79E−09 Cdca8 3.66E−13 0.503278989 0.293 0.011 9.09E−09 Kif4 4.33E−13 0.434892938 0.264 0 1.07E−08 Dbf4 5.83E−13 0.561185724 0.351 0.046 1.45E−08 Cenpe 6.54E−13 0.655143344 0.287 0.011 1.63E−08 Arhgap11a 8.37E−13 0.391036423 0.259 0 2.08E−08 Pcna 8.96E−13 0.612264476 0.414 0.092 2.23E−08 Mcm5 1.48E−12 0.50726949 0.31 0.029 3.67E−08 Map4k4 2.73E−12 0.558455532 0.305 0.029 6.78E−08 Aurkb 5.93E−12 0.413096395 0.241 0 1.47E−07 Ttk 5.93E−12 0.390521577 0.241 0 1.47E−07 Plk1 6.03E−12 0.404527572 0.264 0.011 1.50E−07 Diap3 7.26E−12 0.400030606 0.264 0.011 1.80E−07 Incenp 8.17E−12 0.536649645 0.276 0.017 2.03E−07 Apoa5 8.37E−12 −0.482783443 0.759 0.931 2.08E−07 Neurl1b 8.62E−12 0.423286963 0.253 0.006 2.14E−07 Uox 9.44E−12 −0.499476519 0.856 0.954 2.34E−07 Shcbp1 1.13E−11 0.376352181 0.236 0 2.81E−07 2700094K13Rik 1.52E−11 0.548631981 0.448 0.138 3.79E−07 Calm2 1.76E−11 0.710664504 0.695 0.46 4.36E−07 Kif2c 2.15E−11 0.404282153 0.23 0 5.34E−07 Mcm6 3.26E−11 0.512710004 0.316 0.046 8.09E−07 Aox3 3.32E−11 −0.684717258 0.632 0.851 8.23E−07 Ccnb1 3.71E−11 0.363013517 0.241 0.006 9.21E−07 Car3 4.24E−11 −0.588546974 0.695 0.897 1.05E−06 Rad51 4.34E−11 0.316938048 0.259 0.017 1.08E−06 Hells 4.56E−11 0.404612434 0.247 0.011 1.13E−06 Casc5 6.49E−11 0.511352815 0.236 0.006 1.61E−06 Tyms 8.41E−11 0.462105237 0.362 0.086 2.09E−06 Foxm1 8.70E−11 0.333261782 0.23 0.006 2.16E−06 Elovl3 1.52E−10 −0.63437531 0.259 0.58 3.78E−06 Zwilch 1.70E−10 0.29872803 0.224 0.006 4.21E−06 Ncapg2 2.25E−10 0.341013594 0.259 0.023 5.60E−06 Cdca2 2.72E−10 0.308760405 0.207 0 6.75E−06 Mad2l1 3.19E−10 0.421535724 0.276 0.034 7.93E−06 Mnrnpab 3.20E−10 0.613103641 0.713 0.523 7.95E−06 Cenpm 4.51E−10 0.356059134 0.293 0.046 1.12E−05 Tuba1c 4.87E−10 0.741932397 0.644 0.42 1.21E−05 Tdo2 5.03E−10 −0.43203435 0.856 0.943 1.25E−05 Serpinb8 8.51E−10 0.37625294 0.236 0.017 2.11E−05 Abcb11 9.09E−10 −0.548869051 0.603 0.816 2.26E−05 Stmn1 9.54E−10 0.25333229 0.224 0.011 2.37E−05 Hsd3b5 1.12E−09 −0.663150283 0.184 0.466 2.79E−05 Kif22 1.28E−09 0.326233499 0.218 0.011 3.17E−05 Cdkn2c 1.29E−09 0.414018009 0.282 0.046 3.21E−05 Hjurp 1.34E−09 0.746962345 0.517 0.253 3.33E−05 Rad21 1.71E−09 0.693598694 0.506 0.236 4.24E−05 Plk4 1.79E−09 0.445870522 0.241 0.023 4.45E−05 Hal 1.84E−09 −0.904034035 0.408 0.603 4.58E−05 Cps1 2.12E−09 −0.449845949 0.931 0.96 5.26E−05 Atad2 2.89E−09 0.538790709 0.247 0.029 7.18E−05 Oip5 3.27E−09 0.203934231 0.184 0 8.11E−05 2810408I11Rik 3.72E−09 0.364202374 0.276 0.046 9.23E−05 Apoa1 4.10E−09 −0.266547284 1 1 0.00010193 Ncapd2 4.39E−09 0.272663933 0.207 0.011 0.000109071 Lmnb1 5.28E−09 0.355776415 0.241 0.029 0.000131052 Rbp4 5.80E−09 −0.27547877 0.966 0.994 0.000144054 Sgol2 6.04E−09 0.41927217 0.178 0 0.000149884 Slfn9 6.27E−09 0.443882082 0.23 0.023 0.000155728 Thrsp 6.81E−09 −0.571637606 0.379 0.621 0.000169221 Tmpo 9.73E−09 0.620801056 0.506 0.253 0.000241635 Vars 1.02E−08 0.45501932 0.391 0.132 0.000252944 Mbl2 1.03E−08 0.510840856 0.822 0.736 0.000255976 H2afx 1.34E−08 0.293587722 0.224 0.023 0.000331923 Lig1 1.35E−08 0.399890983 0.224 0.023 0.000335561 Mdc1 1.60E−08 0.349180142 0.282 0.057 0.000398491 Aspm 1.65E−08 0.327831807 0.184 0.006 0.000409937 Dlgap5 1.82E−08 0.324966932 0.184 0.006 0.000451854 Arhgef39 2.04E−08 0.20651116 0.167 0 0.000507222 Fabp1 2.31E−08 −0.329852078 0.977 0.989 0.000574129 Ncaph 2.38E−08 0.319017176 0.207 0.017 0.000591378 Hist1h1b 2.74E−08 0.375177572 0.178 0.006 0.000680526 Hat1 2.94E−08 0.350598047 0.287 0.069 0.000731007 Dnajc9 3.45E−08 0.43096565 0.31 0.08 0.000855729 Fen1 3.71E−08 0.324876638 0.224 0.029 0.000922489 Prr11 3.74E−08 0.242134134 0.161 0 0.000929068 Ska1 3.74E−08 0.231568321 0.161 0 0.000929068 Ywhah 4.02E−08 0.354504609 0.293 0.069 0.000998691 Pecr 4.99E−08 −0.394577277 0.448 0.69 0.001239461 Cdkn2d 5.42E−08 0.258022749 0.218 0.029 0.001344828 Bub1 5.43E−08 0.222527368 0.195 0.017 0.001347871 Comt 5.64E−08 −0.336939912 0.81 0.943 0.001399472 Mlf1ip 5.65E−08 0.29860168 0.172 0.006 0.00140177 Psip1 5.68E−08 0.412140435 0.402 0.155 0.001410087 Ccdc34 6.19E−08 0.450221698 0.27 0.063 0.001537453 Haus4 6.51E−08 0.312841092 0.287 0.069 0.001616969 Alb 6.61E−08 −0.297392831 1 1 0.00164176 Mastl 6.79E−08 0.369179893 0.207 0.023 0.001686689 Mxd3 6.83E−08 0.223725416 0.155 0 0.001696992 Ndc80 8.36E−08 0.276132253 0.167 0.006 0.002076373 Gpx7 8.67E−08 0.222864148 0.184 0.011 0.00215394 Bhmt 8.84E−08 −0.436626346 0.828 0.908 0.002196332 Hn1 1.11E−07 0.35302193 0.293 0.08 0.002746119 Gins2 1.21E−07 0.259574009 0.224 0.034 0.002996965 Tcf19 1.48E−07 0.294242686 0.195 0.023 0.003684451 Mcm8 1.52E−07 0.207497457 0.161 0.006 0.003768811 Dtymk 1.55E−07 0.428448179 0.414 0.178 0.003845818 Kpnb1 1.58E−07 0.642471426 0.598 0.374 0.003919368 Rangap1 1.75E−07 0.497310257 0.54 0.333 0.004336791 Klf6 1.77E−07 0.416981155 0.287 0.075 0.004404128 Ces3b 1.89E−07 −0.468451514 0.368 0.586 0.00469596 Cml2 1.90E−07 −0.420806129 0.741 0.885 0.00472796 Cdkn3 1.92E−07 0.294475986 0.207 0.029 0.004766244 4632434I11Rik 1.99E−07 0.219596415 0.201 0.023 0.004939952 Fignl1 2.26E−07 0.208834541 0.144 0 0.005615642 Rbl1 2.74E−07 0.288971872 0.213 0.034 0.006797795 Hpd 2.75E−07 −0.352708023 0.902 0.931 0.00683379 Selenbp2 2.82E−07 −0.546009344 0.632 0.787 0.006995798 Tk1 2.90E−07 0.36336783 0.339 0.121 0.007199845 Bub1b 3.10E−07 0.254260074 0.155 0.006 0.007691412 Chaf1a 3.45E−07 0.231375382 0.178 0.017 0.008567106 Sae1 3.47E−07 0.394616101 0.437 0.195 0.008620339 Pole3 4.32E−07 0.360643954 0.402 0.172 0.01072822 Ccl9 4.40E−07 0.66722565 0.655 0.448 0.010924443 Cdk5rap2 4.62E−07 0.331940452 0.201 0.029 0.011466687 Scp2 4.81E−07 −0.331704281 0.862 0.954 0.011953871 Suv39h1 4.94E−07 0.290883863 0.178 0.017 0.012257487 Mcm7 5.46E−07 0.361201441 0.276 0.08 0.013549576 Slco1a1 5.51E−07 −0.459298123 0.477 0.678 0.013677968 Gmnn 6.82E−07 0.35501373 0.276 0.08 0.016938424 Mnrnpa2b1 6.92E−07 0.364373341 0.799 0.73 0.017192749 mt-Co1 7.02E−07 −0.448010334 0.925 0.954 0.017435262 Reep4 7.73E−07 0.301442648 0.23 0.052 0.019199816 Hsd17b2 7.95E−07 −0.452371152 0.523 0.695 0.019736346 Upp2 8.61E−07 −0.509440895 0.385 0.575 0.021384944 Hsd17b6 8.67E−07 −0.508243085 0.149 0.368 0.021524829 Bub3 9.18E−07 0.410061599 0.368 0.155 0.022791598 Pdcd4 9.47E−07 −0 480756367 0 374 0 575 0 023527462 Dek 9.93E−07 0.565483667 0.523 0.322 0.02464934 Tubb2a 1.08E−06 0.465591059 0.586 0.374 0.026786812 2810007J24Rik 1.10E−06 −0.446441418 0.632 0.793 0.027231326 Rpa1 1.13E−06 0.370621427 0.391 0.184 0.028159865 Ranbp1 1.16E−06 0.446858539 0.466 0.241 0.02882351 Hsp90aa1 1.18E−06 0.438704989 0.483 0.27 0.029289082 Eri2 1.25E−06 0.236618768 0.19 0.029 0.030953592 Hyls1 1.34E−06 0.272967156 0.126 0 0.033156502 Insig2 1.34E−06 −0.483909727 0.5 0.672 0.033305631 Dhfr 1.49E−06 0.423679824 0.489 0.287 0.037008278 Mybl1 1.52E−06 0.287881605 0.167 0.017 0.037682685 Fam111a 1.72E−06 0.325832889 0.138 0.006 0.042742649 Cenpk 1.80E−06 0.202635563 0.149 0.011 0.044595626 Mthfd2 2.03E−06 0.219619521 0.149 0.011 0.050442715 Ndc1 2.13E−06 0.296534986 0.27 0.08 0.052968483 Etnppl 2.18E−06 −0.484390252 0.178 0.379 0.054221467 Nop58 2.23E−06 0.433692928 0.385 0.178 0.055321793 Rfc4 2.26E−06 0.237784064 0.218 0.046 0.056232628 Mup3 2.36E−06 −0.30602015 1 1 0.058588809 Trim59 2.40E−06 0.229039212 0.121 0 0.059637901 Rad18 2.51E−06 0.261961421 0.161 0.017 0.062371563 Cdo1 2.72E−06 −0.330478369 0.833 0.943 0.067429661 Timm50 2.74E−06 0.385094148 0.408 0.201 0.068009274 Anp32e 2.86E−06 0.300941339 0.351 0.149 0.071040964 Pck1 2.96E−06 −0.348158569 0.92 0.948 0.073458089 Reep6 3.09E−06 −0.370256216 0.621 0.782 0.076699226 Lin54 3.11E−06 0.260601036 0.218 0.052 0.077314843 Xpo1 3.11E−06 0.45065952 0.397 0.19 0.077346963 Haus6 3.17E−06 0.287954493 0.167 0.023 0.078636347 Eri1 3.53E−06 0.374929132 0.333 0.132 0.087545947 Gas2l3 3.85E−06 0.301751089 0.253 0.075 0.095490635 Dut 3.86E−06 0.302722263 0.293 0.103 0.095759296 E2f8 4.41E−06 0.273383207 0.184 0.034 0.109423351 Rnaseh2c 4.74E−06 0.395665408 0.443 0.224 0.11774774 C8a 4.93E−06 −0.348005456 0.782 0.914 0.122504367 Gins1 5.06E−06 0.225027831 0.19 0.034 0.12576907 Ran 5.35E−06 0.442539115 0.414 0.218 0.132864759 mt-Nd2 5.70E−06 −0.339042127 0.954 0.971 0.141510802 Phf5a 5.97E−06 0.330461091 0.385 0.184 0.148154476 Cdkn1b 6.08E−06 0.392627086 0.356 0.161 0.150875433 Gnmt 6.34E−06 −0.235276025 0.977 0.977 0.157376056 Atpif1 6.97E−06 0.400342706 0.385 0.19 0.173069233 Glud1 7.38E−06 −0.282143773 0.891 0.977 0.183294842 Cyp2f2 7.51E−06 −0.612374975 0.471 0.644 0.186415303 Mis18bp1 7.72E−06 0.227536238 0.109 0 0.191659469 Nudc 8.23E−06 0.211503644 0.345 0.144 0.204357248 Setd8 9.03E−06 0.375290352 0.414 0.224 0.22415728 Serpina3n 9.17E−06 0.394742592 0.828 0.77 0.227701048 Tgm2 1.03E−05 0.459985731 0.529 0.345 0.25578588 Serpina1b 1.11E−05 −0.20979262 0.966 0.971 0.276483244 Ybx1 1.12E−05 0.433858711 0.667 0.489 0.278101738 Scd1 1.14E−05 −0.503565027 0.856 0.931 0.282777037 Rpa2 1.18E−05 0.224823858 0.218 0.057 0.292962164 Kmo 1.24E−05 0.384931727 0.799 0.724 0.308137573 H2afv 1.25E−05 0.317443687 0.437 0.23 0.309287953 Cml1 1.25E−05 −0.406306558 0.391 0.592 0.311564113 Pagr1a 1.32E−05 0.277205013 0.224 0.063 0.327068434 Slc38a4 1.32E−05 −0.312113482 0.753 0.862 0.327971723 Srsf3 1.36E−05 0.336110854 0.385 0.201 0.337484189 Rps20 1.37E−05 0.382765037 0.667 0.494 0.339399222 Ublcp1 1.39E−05 0.274341853 0.23 0.069 0.346164244 Malat1 1.41E−05 −0.80879767 0.448 0.667 0.349428979 Snx7 1.46E−05 0.316271647 0.379 0.178 0.361577964 Wbp5 1.51E−05 0.284833036 0.333 0.149 0.375816193 Rfc5 1.55E−05 0.248445785 0.247 0.08 0.38412716 Haao 1.57E−05 −0.31181035 0.695 0.828 0.388664443 Pigr 1.67E−05 −0.440084062 0.787 0.845 0.414812064 Ckap5 1.69E−05 0.217434157 0.259 0.086 0.420108397 Txnrd1 1.73E−05 0.401234639 0.655 0.529 0.429420356 Vrk1 1.74E−05 0.274134129 0.172 0.034 0.4323753 Slc38a3 1.74E−05 −0.361188229 0.701 0.851 0.432795193 G3bp1 1.78E−05 0.375563886 0.362 0.167 0.441399057 Cpn2 1.97E−05 −0.344002539 0.483 0.678 0.489125563 Bhmt2 2.08E−05 −0.37069517 0.443 0.609 0.516393709 Hspa8 2.37E−05 0.340473403 0.77 0.684 0.589258722 7-Sep 2.38E−05 0.455670864 0.517 0.316 0.589819559 Rfc2 2.45E−05 0.360830553 0.31 0.138 0.608206199 Ppil1 2.45E−05 0.227042373 0.259 0.092 0.608514071 Dctpp1 2.58E−05 0.35767839 0.397 0.207 0.640693109 Mcm2 2.64E−05 0.285279656 0.19 0.046 0.654386851 Rpn2 2.71E−05 0.405358032 0.569 0.408 0.67281896 Ube2k 2.83E−05 0.348055395 0.517 0.31 0.703678327 Mbd1 2.87E−05 0.364824514 0.333 0.149 0.713355213 Ndrg2 3.23E−05 −0.296808072 0.868 0.931 0.80182229 Srxn1 3.67E−05 0.319778489 0.379 0.195 0.912373853 Calm3 3.76E−05 0.432242817 0.385 0.213 0.933445302 Rnaseh2b 4.08E−05 0.217676579 0.213 0.063 1 Mat2a 4.11E−05 0.482635376 0.471 0.305 1 Atf3 4.15E−05 0.362943833 0.425 0.218 1 Nfatc2ip 4.47E−05 0.200297983 0.132 0.017 1 Gpd1 4.48E−05 −0.29447894 0.466 0.649 1 G2e3 4.53E−05 0.272666918 0.201 0.057 1 Fgg 4.69E−05 −0.203445263 0.994 1 1 Mlec 4.74E−05 0.490588829 0.621 0.483 1 Ces2a 4.90E−05 −0.273049604 0.592 0.787 1 Lap3 5.10E−05 −0.274273748 0.638 0.782 1 Tmem53 5.34E−05 0.281369697 0.339 0.161 1 Asl 5.78E−05 −0.383514121 0.603 0.776 1 Tcp1 6.52E−05 0.381115369 0.621 0.477 1 Brca2 6.77E−05 0.311589577 0.138 0.023 1 Otc 6.95E−05 −0.283470665 0.805 0.868 1 Sds 7.30E−05 −0.536793811 0.247 0.408 1 Snrpd1 7.67E−05 0.27940919 0.282 0.121 1 Prtn3 7.78E−05 0.284555077 0.27 0.109 1 Hp1bp3 7.93E−05 0.466899479 0.511 0.351 1 Cat 7.96E−05 −0.248150835 0.925 0.948 1 Snrpa1 7.97E−05 0.263512181 0.305 0.138 1 Hn1l 8.32E−05 0.226911148 0.299 0.132 1 Egfr 8.33E−05 −0.261805449 0.81 0.862 1 Pcnt 8.62E−05 0.226629309 0.149 0.029 1 Pgp 8.70E−05 0.275068866 0.374 0.207 1 Ldha 8.93E−05 0.297270276 0.891 0.851 1 Gstm3 9.25E−05 0.669387901 0.598 0.42 1 Ccnf 9.40E−05 0.268249638 0.253 0.098 1 Hmgcs2 9.40E−05 −0.266526208 0.868 0.914 1 Ccdc77 9.48E−05 0.286413022 0.201 0.063 1 Cbx5 0.000100141 0.36710943 0.356 0.19 1 Tgoln1 0.000102696 −0.325934331 0.414 0.569 1 Rps11 0.000102835 0.365440855 0.489 0.316 1 Mdh1 0.000104647 −0.290065525 0.747 0.874 1 Nubp1 0.000105157 0.381850948 0.379 0.213 1 F7 0.000108949 −0.400251784 0.425 0.569 1 Smad4 0.000111273 0.253879461 0.351 0.172 1 Adck3 0.000114764 −0.374339709 0.54 0.638 1 Tprkb 0.000117286 −0.299935577 0.339 0.506 1 Slc25a48 0.000117538 0.381303403 0.253 0.103 1 Hspa14 0.000117567 0.271589342 0.339 0.172 1 Azgp1 0.000122515 −0.242890214 0.92 0.971 1 Tcirg1 0.000123612 0.200461262 0.27 0.109 1 Cyp2d26 0.000125749 −0.291556913 0.753 0.81 1 Cenpl 0.000131986 0.266357687 0.218 0.075 1 Mug2 0.000132583 −0.405169711 0.58 0.713 1 Agxt 0.000139728 −0.39457087 0.529 0.661 1 Mdm2 0.000153218 0.340634023 0.322 0.161 1 Snrnp48 0.000154667 0.204158168 0.224 0.086 1 Mrps6 0.000155642 0.310188333 0.253 0.109 1 Nup205 0.000159713 0.261616453 0.213 0.075 1 Aldh1l1 0.000160944 −0.253939008 0.862 0.931 1 Serpina1d 0.000167571 −0.259689069 0.868 0.943 1 Emc8 0.000168202 0.231906188 0.333 0.167 1 Ccng1 0.00016908 0.295124571 0.356 0.19 1 Anp32b 0.000176313 0.396891769 0.448 0.299 1 Ykt6 0.000180442 0.380489397 0.351 0.195 1 Nags 0.000184693 0.338438646 0.466 0.282 1 Slc27a2 0.000184889 −0.252814105 0.845 0.92 1 Gls2 0.000185814 −0.326680339 0.402 0.586 1 Hist1h1e 0.000188497 0.244826085 0.224 0.08 1 Afm 0.000191908 −0.290504337 0.466 0.621 1 Zfp367 0.000193424 0.263894736 0.264 0.115 1 Wfdc17 0.000208137 0.287356386 0.19 0.057 1 Pola1 0.000213231 0.244320999 0.155 0.04 1 Ptma 0.000218547 0.21952298 0.27 0.121 1 Lgals9 0.000228862 −0.329391013 0.638 0.753 1 mt-Cytb 0.000232534 −0.255568848 0.902 0.937 1 Tkt 0.000234475 0.344836871 0.552 0.402 1 Ppp4c 0.000234501 0.251294639 0.236 0.092 1 Tmem97 0.000242512 0.400583107 0.46 0.299 1 Apob 0.000245863 −0.299875775 0.977 0.966 1 Tpr 0.000251283 0.456623718 0.523 0.379 1 Gm2788 0.000271859 −0.211472801 0.092 0.23 1 Scaf11 0.000279695 0.292403074 0.437 0.27 1 Clcc1 0.000279736 0.28298206 0.379 0.213 1 Csrp2 0.000298218 0.28424465 0.322 0.161 1 Ccbl2 0.000299733 −0.300791814 0.443 0.586 1 Rgn 0.000301617 0.20528053 0.931 0.77 1 Psmb1 0.000307241 0.286652401 0.713 0.626 1 Snx5 0.000307539 0.239409221 0.391 0.224 1 Cd5l 0.000313116 0.45974441 0.218 0.08 1 Ptp4a2 0.000320524 0.310982553 0.632 0.5 1 Rpl13a 0.000327249 0.278346993 0.799 0.747 1 Idh1 0.00033107 −0.290981994 0.661 0.793 1 Mcm3 0.000341799 0.235971207 0.172 0.052 1 Exosc8 0.000344627 0.250463363 0.247 0.103 1 Hgd 0.000355827 −0.254976188 0.644 0.81 1 Pdik1l 0.000355912 0.273144229 0.224 0.092 1 Gsr 0.000358394 0.23781591 0.489 0.316 1 Atp6v1c1 0.00036526 0.347468443 0.345 0.195 1 Lpin1 0.000399187 −0.352223257 0.207 0.356 1 Gjb2 0.000401614 −0.280030843 0.546 0.678 1 Cby1 0.000404829 0.217990914 0.195 0.069 1 Ssx2ip 0.000412834 0.214346928 0.207 0.08 1 Rrbp1 0.000430781 −0.271973566 0.73 0.793 1 Arf6 0.000433644 0.313882002 0.397 0.236 1 Dgat2 0.000435033 −0.228770348 0.621 0.724 1 Rbbp8 0.000438587 0.302400414 0.213 0.086 1 Lsm2 0.000454397 0.249449387 0.241 0.103 1 Vbp1 0.000456079 0.276953076 0.247 0.109 1 Taf9 0.000463719 0.292774574 0.345 0.19 1 Gclc 0.000486647 0.358953864 0.724 0.632 1 Fxn 0.000498295 0.207127367 0.218 0.086 1 Luc7l3 0.000504815 0.276290665 0.374 0.218 1 Gstm1 0.000520109 0.330492518 0.879 0.897 1 Psmc1 0.000526832 0.307490063 0.569 0.414 1 Ilf3 0.000535316 0.223647749 0.282 0.132 1 Kynu 0.000551235 −0.298905085 0.425 0.569 1 Hrsp12 0.000553455 −0.308816674 0.736 0.822 1 Matr3 0.000554487 0.350299293 0.46 0.316 1 Trp53inp1 0.000556941 0.362824706 0.529 0.402 1 Chd1l 0.000559277 0.265372607 0.236 0.103 1 Rbbp7 0.000560518 0.231563045 0.402 0.241 1 Sfpq 0.000561829 0.38724728 0.437 0.282 1 F10 0.00057882 −0.207677398 0.822 0.902 1 Nono 0.000580189 0.242303202 0.293 0.149 1 Mup7 0.00058141 −0.321619611 0.943 0.977 1 Lifr 0.000581781 −0.280666669 0.5 0.638 1 Fam25c 0.000599837 0.25164092 0.667 0.494 1 Ephx1 0.000600839 0.280611043 0.724 0.644 1 Anapc1 0.000607883 0.206380812 0.27 0.126 1 Tinf2 0.000607904 0.20827297 0.172 0.057 1 Pih1d1 0.000628092 0.273760415 0.339 0.184 1 Abca8a 0.000637377 −0.260277819 0.149 0.287 1 Hoga1 0.000663082 −0.273858244 0.385 0.511 1 Aldh1b1 0.0006771 −0.249178685 0.046 0.155 1 Lmna 0.000679483 0.326326742 0.356 0.224 1 Cnot6 0.00069247 0.343829212 0.402 0.264 1 Ncaph2 0.000721239 0.275618301 0.443 0.293 1 Lbr 0.000745604 0.272446091 0.259 0.121 1 Npm1 0.000758444 0.29098559 0.431 0.282 1 Kpna4 0.000768146 0.283598161 0.333 0.19 1 Ctr9 0.000769461 0.317614844 0.333 0.184 1 Upb1 0.000782909 −0.283983501 0.563 0.69 1 Sephs2 0.000827697 −0.259638362 0.753 0.845 1 Ssrp1 0.000834114 0.398030517 0.477 0.322 1 Slc2a2 0.000863816 −0.319257104 0.27 0.414 1 Mt1 0.000867867 0.30883204 0.77 0.649 1 Mug1 0.000886085 −0.252219139 0.908 0.92 1 Serpina12 0.000904201 −0.439014517 0.161 0.287 1 0610005C13Rik 0.000950132 −0.289522779 0.5 0.644 1 D230025D16Rik 0.000950291 0.31895727 0.305 0.167 1 Naa50 0.000993554 0.352403593 0.517 0.385 1 Kif1b 0.001005797 −0.322074636 0.316 0.466 1 Snrnp70 0.001007289 0.231363362 0.414 0.247 1 Psmd7 0.001016916 0.315581184 0.575 0.448 1 Uspl1 0.001037787 0.25033896 0.224 0.098 1 Cdc27 0.001041649 0.225305361 0.305 0.161 1 Cpsf2 0.001048602 0.228178906 0.293 0.155 1 Usp33 0.00105181 0.432922416 0.27 0.138 1 Idh2 0.001053091 0.334148106 0.529 0.397 1 Gpcpd1 0.001082717 −0.21025995 0.253 0.408 1 Slc37a4 0.001123966 −0.359457571 0.276 0.414 1 Hagh 0.001130016 −0.22804631 0.707 0.816 1 Maob 0.001142494 −0.31742738 0.414 0.546 1 Set 0.001187474 0.254464638 0.374 0.23 1 Ccne2 0.001209984 0.26317126 0.126 0.034 1 Brk1 0.001215299 0.283487053 0.379 0.236 1 Mrps16 0.001227646 0.211425725 0.287 0.149 1 Pycrl 0.001231949 0.223192893 0.31 0.172 1 Fnbp1l 0.001251014 0.220422078 0.236 0.109 1 Ces1e 0.00126714 −0.364635829 0.385 0.511 1 Ilf2 0.001274235 0.255415152 0.241 0.115 1 Fam96a 0.001315416 0.312612603 0.425 0.287 1 Whsc1 0.001331048 0.318759797 0.356 0.218 1 Dnajc10 0.001376642 0.246821061 0.368 0.218 1 Lasp1 0.001377399 0.390083334 0.46 0.328 1 Ddx39 0.001378811 0.2103436 0.224 0.103 1 Pnpo 0.00147794 −0.309003494 0.471 0.603 1 Rps3 0.001492324 0.212551746 0.851 0.816 1 Sfmbt1 0.001558217 0.332239288 0.345 0.213 1 Blvrb 0.00157909 0.234388003 0.557 0.402 1 Cebpa 0.001599697 −0.254983029 0.397 0.534 1 mt-Nd5 0.001604259 −0.276002669 0.816 0.891 1 Glo1 0.001626667 −0.292423358 0.517 0.621 1 Cyp3a25 0.001638407 −0.201190406 0.718 0.81 1 Rpl38 0.001655339 0.231403686 0.218 0.103 1 Haus3 0.001674455 0.209827476 0.172 0.069 1 Hsd11b1 0.001710332 −0.353381526 0.621 0.718 1 Mrpl49 0.001820085 0.294845923 0.299 0.178 1 Otud6b 0.001827373 0.277520557 0.27 0.144 1 Mup20 0.001879628 −0.434017754 0.971 0.983 1 Acsl1 0.001921669 −0.27480221 0.649 0.764 1 Nsmce4a 0.001927311 0.223811104 0.322 0.19 1 Tial1 0.001978044 0.253959367 0.351 0.207 1 Rps7 0.001987208 0.202699839 0.207 0.092 1 Polr2f 0.002003606 0.232539505 0.385 0.247 1 Snrpd2 0.002104173 0.246589047 0.351 0.213 1 Clock 0.002251358 0.294489034 0.328 0.201 1 Pold3 0.002292673 0.222109813 0.195 0.086 1 Snrpe 0.002301841 0.224562608 0.305 0.172 1 Mrpl51 0.002347961 0.215486219 0.345 0.213 1 Gm4951 0.002357136 −0.305065865 0.368 0.494 1 Myo10 0.002366423 0.246835424 0.282 0.149 1 Rcbtb2 0.002377524 0.238247244 0.282 0.155 1 Pipox 0.002416454 −0.240575227 0.368 0.523 1 Usp1 0.002481682 0.275810344 0.282 0.161 1 Mup14 0.002489042 −0.27120183 0.494 0.592 1 Rpl37a 0.002496318 0.256856261 0.339 0.207 1 Acot1 0.002509249 0.201537266 0.253 0.132 1 Suz12 0.002526887 0.280277593 0.31 0.178 1 Srrt 0.002534186 0.305896175 0.328 0.207 1 Mup19 0.002541541 −0.467484608 0.557 0.632 1 Myo1c 0.002559313 0.300308227 0.247 0.132 1 Cds2 0.002587388 0.279313685 0.379 0.236 1 Ncl 0.002633004 0.316865625 0.655 0.575 1 Stip1 0.002659945 0.28315643 0.483 0.379 1 Hnrnpul1 0.002768498 0.244806598 0.391 0.264 1 Adss 0.00277119 0.30177346 0.385 0.259 1 Rps19 0.002848401 0.249356214 0.575 0.448 1 Eny2 0.002862696 0.261236803 0.5 0.362 1 Krt8 0.002887003 0.274896508 0.621 0.489 1 Mpv17l2 0.00292474 0.202123451 0.201 0.092 1 Impad1 0.002949531 0.326238567 0.402 0.282 1 Ugdh 0.002968487 0.275976493 0.678 0.603 1 Cth 0.003053485 −0.235854448 0.644 0.77 1 Rps2 0.00308072 0.226119282 0.661 0.557 1 Lman1 0.003235144 −0.276383183 0.58 0.69 1 Ebp 0.003249538 0.276578351 0.695 0.592 1 Timm9 0.003272703 0.246436845 0.328 0.201 1 Caprin1 0.00327566 0.310159837 0.644 0.557 1 Mup6 0.003278638 −0.363001459 0.534 0.598 1 Mmgt1 0.003323514 0.277568508 0.218 0.109 1 Cdc42bpa 0.003337449 0.296302291 0.27 0.149 1 Gys2 0.003345786 −0.266618519 0.247 0.362 1 Tat 0.003362872 −0.204446885 0.891 0.948 1 Arrdc3 0.003390694 −0.274084677 0.201 0.328 1 Decr2 0.003429858 −0.248515355 0.471 0.58 1 Fcna 0.003546657 0.200314485 0.126 0.04 1 Hspa4l 0.003555845 0.224225179 0.356 0.224 1 Faah 0.003590172 0.223244291 0.511 0.362 1 Dynll1 0.003631033 0.356189012 0.385 0.264 1 Inmt 0.003640717 −0.256091272 0.684 0.793 1 Smc1a 0.003667723 0.26846514 0.362 0.236 1 Mrps18a 0.003669283 0.305636501 0.282 0.161 1 Abhd6 0.003692342 0.230830064 0.368 0.236 1 Cyp2c44 0.003724799 −0.240647157 0.46 0.58 1 Uroc1 0.003743767 −0.284923771 0.517 0.609 1 Marco 0.003872675 0.460163442 0.149 0.057 1 Uchl5 0.003891665 0.217812028 0.305 0.19 1 Hamp 0.003937766 0.278788719 0.718 0.609 1 Pter 0.003955936 −0.298749309 0.264 0.385 1 Insig1 0.004042461 −0.246565903 0.443 0.563 1 Cd302 0.004054903 0.216831932 0.879 0.868 1 Ctsc 0.004072786 −0.224783491 0.19 0.316 1 Med19 0.00426259 0.219441046 0.236 0.126 1 Bckdha 0.004281843 −0.244274663 0.42 0.517 1 Serinc3 0.004310832 0.234132553 0.494 0.379 1 Saa4 0.004348051 −0.261762833 0.753 0.81 1 Gpr108 0.004425151 −0.22603556 0.115 0.218 1 Cmah 0.004429229 −0.212506919 0.385 0.523 1 Mocs2 0.004501388 −0.203503301 0.517 0.598 1 Slc7a2 0.004632074 −0.317210502 0.598 0.713 1 Strap 0.004743896 0.228584031 0.466 0.339 1 Clec4f 0.004797027 0.23190205 0.218 0.109 1 Rpl22 0.004937805 0.275204914 0.546 0.42 1 Elp5 0.004998547 0.209886016 0.218 0.109 1 Serpina3m 0.005024551 0.243811964 0.77 0.77 1 Ywhag 0.005074343 0.288452561 0.517 0.414 1 Arpc1b 0.00508026 0.245172175 0.305 0.178 1 Nptn 0.005127487 0.287320757 0.339 0.213 1 Ces1b 0.005217312 0.200087271 0.494 0.374 1 Pdxk 0.005251936 0.243284689 0.23 0.121 1 Dpy30 0.005500491 0.216655337 0.316 0.19 1 1810037I17Rik 0.005778623 0.211310694 0.345 0.218 1 Rbbp4 0.005932398 0.310895251 0.477 0.356 1 Snord13 0.006012681 0.417208326 0.46 0.333 1 Csf1r 0.006160528 0.260730004 0.132 0.046 1 Nicn1 0.006222528 0.226145504 0.236 0.126 1 Mup12 0.006246858 −0.441572158 0.489 0.569 1 Coq2 0.006338538 0.228017679 0.328 0.213 1 Yme1l1 0.006361678 0.223955561 0.575 0.448 1 Opa3 0.006456608 0.275149939 0.345 0.224 1 Atp2c1 0.006528816 0.218202897 0.259 0.144 1 Sun2 0.006773287 0.244395261 0.368 0.247 1 Sar1b 0.006796779 −0.238677843 0.5 0.621 1 Cenpb 0.007197198 0.29209786 0.379 0.27 1 Ftcd 0.007254799 −0.236915896 0.517 0.603 1 Calu 0.007575412 0.204995826 0.391 0.264 1 Il1rap 0.007778177 −0.302722178 0.374 0.477 1 Psmc5 0.008043174 0.213987203 0.557 0.414 1 Smarcc1 0.0080442 0.207630543 0.345 0.23 1 Actb 0.008170796 0.20065238 0.902 0.96 1 Rnf141 0.008612042 0.243430584 0.374 0.259 1 Hint1 0.008673406 0.278109318 0.753 0.73 1 Plxna2 0.00875936 −0.211045239 0.052 0.132 1 Csad 0.008778135 0.237189009 0.557 0.431 1 Gtf3c4 0.008803983 0.200525731 0.218 0.115 1 Apex1 0.008816562 0.247646366 0.27 0.161 1 Slc40a1 0.008850796 0.28276667 0.391 0.259 1 B230219D22Rik 0.008870372 0.21573072 0.345 0.218 1 Rps5 0.008922041 0.308634542 0.839 0.845 1 Mup4 0.008927704 −0.278610154 0.305 0.402 1 Aqp8 0.008944689 −0.248202502 0.259 0.374 1 Sh3bgrl 0.008960366 0.304384057 0.557 0.414 1 Cxcl1 0.009048319 −0.30974824 0.368 0.489 1 Acad11 0.0091016 −0.279085199 0.397 0.5 1 Os9 0.009262437 −0.241560677 0.523 0.632 1 Cct2 0.009296317 0.26056313 0.609 0.506 1 Slc17a2 0.009411837 −0.225152117 0.299 0.408 1 Pcyt2 0.009491776 −0.265725588 0.46 0.603 1 Cacybp 0.009506321 0.208121446 0.356 0.236 1 H3f3b 0.009520983 0.242133513 0.54 0.454 1 Cpped1 0.009650292 0.245780009 0.425 0.31 1 Arpc4 0.009701026 0.244147674 0.299 0.195 1 mt-Nd4 0.009806959 −0.330562447 0.851 0.868 1 Cyp2d9 0.009863302 −0.21251377 0.764 0.885 1 Brd7 0.01022504 0.24880251 0.31 0.201 1 Lmo4 0.01042178 0.230146494 0.224 0.121 1 Mrpl18 0.010449979 0.271017845 0.385 0.27 1 Mnrnpl 0.010478934 0.20130563 0.333 0.224 1 Ndufb10 0.010581051 −0.230971243 0.557 0.644 1 Hdgf 0.011006886 0.298205008 0.552 0.477 1 Ndufb7 0.011093102 0.281504386 0.569 0.454 1 Kras 0.011161828 0.239901841 0.328 0.218 1 Mrpl33 0.011165541 0.295337683 0.443 0.345 1 Gstm2 0.011172361 0.209182349 0.385 0.259 1 Dap3 0.011395912 0.310029486 0.345 0.241 1 Atl2 0.011399898 0.28646695 0.379 0.264 1 Rpl26 0.011418585 0.302442081 0.632 0.523 1 Abcb6 0.011429815 0.280241248 0.385 0.27 1 Lipa 0.011468112 0.200015494 0.684 0.603 1 Banf1 0.01186588 0.236631164 0.356 0.253 1 Orm2 0.011955778 0.216695694 0.695 0.575 1 Tmsb4x 0.012156792 0.352694664 0.241 0.138 1 Leap2 0.012207481 −0.300816683 0.408 0.517 1 Casp8 0.012221596 0.213097538 0.236 0.138 1 Srsf1 0.012357324 0.274604273 0.356 0.247 1 Khk 0.012440505 −0.249137231 0.678 0.741 1 Carhsp1 0.012531079 0.319710888 0.379 0.299 1 Slc25a10 0.012542423 0.207832074 0.529 0.408 1 Dis3l 0.01263226 0.218699045 0.213 0.121 1 Vps36 0.012987505 0.274038809 0.339 0.236 1 Qdpr 0.013483198 −0.211506384 0.713 0.747 1 Dnm1l 0.013510207 0.234951606 0.362 0.259 1 Hpgd 0.013665829 0.226866333 0.425 0.322 1 Triap1 0.013715135 0.206958913 0.207 0.115 1 Ddah1 0.013913907 −0.229307183 0.322 0.443 1 Rhod 0.014224771 0.203809463 0.282 0.184 1 Mcm10 0.014232039 −0.232484957 0.224 0.322 1 Ibtk 0.014339165 0.230852193 0.391 0.276 1 Immt 0.014527035 0.314198334 0.517 0.414 1 Slc22a30 0.014677509 −0.251268208 0.328 0.425 1 Nudcd2 0.014812869 0.248670133 0.328 0.23 1 Nsmce1 0.01486159 0.252864026 0.322 0.224 1 Cpne3 0.015250747 0.294236673 0.511 0.402 1 Slc3a2 0.015808689 0.219634219 0.236 0.144 1 Fam210b 0.01604669 −0.22593416 0.397 0.5 1 Hspd1 0.016067675 0.23534371 0.615 0.557 1 Adipor2 0.016193716 −0.257034087 0.718 0.776 1 Oat 0.016305262 0.292703373 0.5 0.397 1 Gnai2 0.016596229 0.256616592 0.466 0.339 1 Mob3b 0.016709013 0.211167706 0.236 0.144 1 Sumo3 0.016883831 0.295186967 0.471 0.391 1 2700060E02Rik 0.016991549 0.246273177 0.408 0.305 1 Pbld1 0.016999839 −0.200773785 0.339 0.431 1 Ctcf 0.017060197 0.29778649 0.293 0.195 1 Tmx2 0.017182975 0.208652952 0.322 0.224 1 Eif6 0.017376562 0.220475649 0.408 0.31 1 Saa1 0.017409969 0.235927452 0.937 0.879 1 Gm6484 0.017707724 −0.239084424 0.103 0.184 1 Ppp2r5e 0.017731156 0.213917029 0.362 0.264 1 Rps27l 0.017839688 0.259957822 0.701 0.672 1 Shoc2 0.0179067 0.227313307 0.339 0.23 1 Rdh11 0.017989816 0.234866085 0.443 0.339 1 Fbxo30 0.018061788 0.247683896 0.167 0.086 1 Pds5a 0.018213315 0.2096822 0.264 0.167 1 Nfyb 0.018514036 0.201736814 0.27 0.172 1 Rpl36al 0.01867848 0.227430291 0.511 0.414 1 Dpyd 0.018939626 −0.207660551 0.494 0.598 1 Keap1 0.019209184 0.224305051 0.402 0.293 1 Gzf1 0.019213526 0.294348759 0.339 0.236 1 Gfm1 0.019244456 0.206633144 0.425 0.322 1 Mbd3 0.019279057 0.262066315 0.379 0.282 1 Gapvd1 0.019311281 0.223374216 0.293 0.195 1 Txn2 0.019513804 −0.205404835 0.46 0.557 1 Sgk2 0.019702868 −0.281901472 0.195 0.287 1 Mrpl48 0.019837016 0.203084366 0.224 0.132 1 Hebp1 0.020095167 −0.21588023 0.546 0.644 1 Arpp19 0.020184043 0.248525375 0.471 0.368 1 G3bp2 0.020214404 0.254441829 0.477 0.374 1 D17Wsu92e 0.020375994 0.258509249 0.598 0.563 1 Prkd3 0.020437553 −0.230881843 0.431 0.529 1 Lcn2 0.020792109 0.206498859 0.667 0.534 1 Wapal 0.020803332 0.23807797 0.517 0.42 1 Cct5 0.020920087 0.285043345 0.603 0.534 1 Retsat 0.021162383 −0.327711821 0.511 0.557 1 Saa2 0.021583651 0.251309011 0.77 0.724 1 Szrd1 0.021627753 0.220282685 0.385 0.282 1 Etnk2 0.021720372 −0.243330541 0.546 0.609 1 Eef1d 0.02187914 0.247282181 0.437 0.339 1 Nup88 0.022150869 0.24232933 0.218 0.132 1 Psmd2 0.022305574 0.243358975 0.511 0.443 1 Fkbp2 0.022625189 0.250554432 0.546 0.437 1 Dnajc22 0.022643266 0.26166465 0.552 0.494 1 Blvra 0.022971107 0.242991088 0.253 0.161 1 Hsd3b3 0.023233447 −0.258431285 0.425 0.517 1 Dpp4 0.023405669 0.203659148 0.454 0.356 1 Tmem106b 0.023617735 −0.230722925 0.448 0.523 1 Akr1c19 0.023755169 0.23338723 0.466 0.362 1 Egr1 0.023819407 0.220517026 0.494 0.414 1 Sppl2a 0.023896904 0.225826218 0.615 0.506 1 Map1lc3b 0.023897255 −0.207314779 0.264 0.356 1 Wdr48 0.024293713 0.21960522 0.27 0.184 1 Dpys 0.024446167 −0.256803998 0.466 0.534 1 Eif3h 0.024456091 0.294440454 0.575 0.506 1 Rer1 0.024496578 0.226471902 0.431 0.339 1 Zfp91 0.024540292 0.251453484 0.546 0.466 1 Utp3 0.024843557 0.265694599 0.362 0.259 1 Dhx15 0.024933924 0.300789082 0.368 0.276 1 Syne2 0.025020753 0.221539341 0.287 0.19 1 Txndc9 0.025204473 0.320248454 0.287 0.195 1 H2afy 0.025209744 0.208626457 0.529 0.437 1 Abat 0.025345228 −0.240152398 0.58 0.649 1 Ndufa8 0.025803507 0.205315445 0.615 0.517 1 Atg12 0.026361167 0.216199712 0.31 0.213 1 Mnrnpm 0.026509991 0.237984435 0.362 0.282 1 Ipo5 0.026527598 0.209133978 0.276 0.19 1 Mycbp 0.026954934 0.203356679 0.264 0.172 1 Mt2 0.026971886 0.31805591 0.695 0.609 1 Dnajc2 0.027055074 0.203873598 0.236 0.149 1 Cwf19l2 0.02729564 0.250617416 0.201 0.121 1 Hibch 0.027978397 −0.286834561 0.276 0.374 1 Dsp 0.028292845 −0.24308704 0.19 0.282 1 Exoc4 0.028722276 0.270709894 0.293 0.201 1 Sorbs2 0.028909173 0.213041815 0.397 0.299 1 Rps18 0.028943546 0.202877972 0.632 0.529 1 Fxr2 0.029093243 0.268694616 0.213 0.126 1 Hras 0.030100817 0.299616126 0.431 0.356 1 Tcf4 0.030183418 0.201428644 0.149 0.08 1 Rpl3 0.030330012 0.292268532 0.391 0.293 1 Mrpl54 0.030987433 0.211022994 0.339 0.241 1 Copz1 0.031526118 −0.286190248 0.374 0.46 1 Lrpprc 0.033102616 −0.236064383 0.385 0.477 1 Ndufs6 0.03506636 0.215815094 0.598 0.529 1 Aim1 0.035806526 0.219520531 0.287 0.195 1 Saa3 0.036302206 0.577607147 0.391 0.299 1 Lrrc58 0.036390449 −0.240695487 0.333 0.431 1 Decr1 0.036405359 −0.215322531 0.517 0.615 1 Spag9 0.036695211 −0.212359016 0.282 0.379 1 Tmed7 0.037888709 −0.205329015 0.414 0.483 1 Entpd5 0.038227053 0.210104663 0.621 0.557 1 Tcerg1 0.038897924 0.267832269 0.195 0.121 1 Acsf2 0.038897924 −0.219388645 0.121 0.195 1 Sptssa 0.038938052 0.222943638 0.443 0.351 1 Ap3b1 0.039319143 0.301743969 0.362 0.276 1 Pbf14 0.040853389 0.246441091 0.236 0.149 1 Mfn2 0.04092404 0.2025045 0.391 0.305 1 Gfer 0.042628023 0.240942535 0.339 0.259 1 Nfia 0.043029792 0.211281834 0.374 0.282 1 Trappc13 0.043101637 0.217746706 0.259 0.178 1 Tbl1x 0.043601109 0.204898253 0.402 0.31 1 Msl3 0.045102788 0.236211559 0.247 0.167 1 Efna1 0.045838317 −0.205634717 0.305 0.379 1 Nipsnap1 0.046051269 −0.220923712 0.615 0.661 1 Magt1 0.046203205 −0.211713805 0.402 0.466 1 Ddt 0.046305466 0.206340801 0.672 0.615 1 Ndufa11 0.046330307 0.229735966 0.443 0.362 1 C1qb 0.046414021 0.391357306 0.167 0.098 1 Myh10 0.046442872 0.243905291 0.218 0.144 1 Rpl39 0.046825507 0.220871962 0.437 0.362 1 Cdc34 0.046827233 0.244606779 0.534 0.471 1 Tstd2 0.047364738 0.222703062 0.195 0.121 1 Aldh6a1 0.047461614 −0.235184768 0.54 0.603 1 Anp32a 0.047479235 0.247594131 0.408 0.333 1 Serpinf1 0.047490175 −0.20019453 0.713 0.73 1 Gm24601 0.048145145 0.231716349 0.391 0.293 1 BC005537 0.048785835 0.298901807 0.5 0.42 1 Sfxn1 0.049152777 −0.240207413 0.402 0.471 1 Fubp1 0.049710915 0.203229491 0.241 0.167 1 Mnrnpc 0.050896017 0.200044122 0.448 0.351 1 Grip2 0.051111051 −0.619607732 0.149 0.236 1 Cnot1 0.051175552 0.218985315 0.31 0.23 1 Ggnbp2 0.051982034 0.21529549 0.471 0.368 1 Gss 0.052057686 0.22604635 0.454 0.374 1 Aspg 0.052401512 −0.222298996 0.224 0.287 1 Chd8 0.052401541 0.242974398 0.299 0.213 1 Uqcr10 0.053864701 0.264431516 0.718 0.644 1 Lyz2 0.054277151 0.29805528 0.167 0.098 1 Trpc4ap 0.056052262 0.2138402 0.293 0.218 1 Specc1l 0.056478111 0.218824052 0.161 0.098 1 Cd163 0.057321755 0.269431124 0.098 0.046 1 Cldn2 0.057579448 −0.215656114 0.236 0.305 1 Cd2ap 0.05768152 0.23579619 0.276 0.201 1 Qser1 0.057690417 0.283756443 0.213 0.144 1 Mup1 0.058856335 −0.208101355 0.397 0.46 1 Cisd2 0.060516248 0.208851947 0.42 0.333 1 Casp3 0.062306591 0.210912344 0.259 0.19 1 Stub1 0.062888331 0.224769038 0.414 0.356 1 Adrbk1 0.063207706 0.206901175 0.155 0.092 1 Gm10800 0.065789182 −0.295424977 0.023 0.063 1 Vapa 0.065815815 0.211922971 0.397 0.305 1 Ndufaf2 0.066094467 0.208054391 0.339 0.264 1 Gch1 0.06613008 0.207064291 0.557 0.511 1 Mxd4 0.066182986 −0.224203201 0.224 0.293 1 Tor1b 0.066283436 0.214789628 0.27 0.201 1 Deptor 0.068470633 −0.219528623 0.397 0.46 1 Eif3d 0.068969412 0.212677163 0.42 0.351 1 Cfl2 0.069774684 0.204527974 0.414 0.351 1 Dnm2 0.069841224 0.201366691 0.287 0.213 1 2810004N23Rik 0.071267147 0.279868496 0.351 0.27 1 Mrpl20 0.073361269 0.207221171 0.466 0.391 1 Ildr2 0.074426769 0.34186496 0.333 0.27 1 Gars 0.077067731 0.213365361 0.293 0.224 1 Ctnnd1 0.077946124 0.231250746 0.339 0.259 1 A1cf 0.078522619 0.214908799 0.5 0.443 1 Nmt2 0.082282004 0.207030081 0.218 0.155 1 Rps24 0.083491925 0.240979347 0.632 0.569 1 Ndufa3 0.085532305 −0.205539056 0.483 0.552 1 Ces1g 0.086135024 0.228893144 0.517 0.477 1 Cops3 0.088068119 0.222657556 0.362 0.287 1 Arid4b 0.088454061 0.22799984 0.236 0.172 1 Litaf 0.093099022 0.222901848 0.425 0.339 1 Polr3c 0.093769073 0.216488984 0.23 0.161 1 Chordc1 0.094283632 0.24072197 0.374 0.287 1 Anapc13 0.094582243 0.201825147 0.425 0.356 1 Rpph1 0.098448086 0.202132446 0.23 0.167 1 Mup9 0.099745235 −0.271781283 0.368 0.443 1 Eif5b 0.10119655 0.218495171 0.443 0.362 1 Trpm7 0.101862919 0.224519601 0.345 0.27 1 Gsto1 0.102193646 −0.242358799 0.322 0.374 1 Hbb-bs 0.103010489 −0.208517986 0.075 0.126 1 Zfp191 0.103122269 0.223545853 0.282 0.213 1 Rock1 0.104733377 0.251852561 0.362 0.31 1 Trmt2a 0.10631232 0.201837146 0.155 0.098 1 Hmgn5 0.108114199 0.200609931 0.379 0.316 1 Mrpl13 0.110202369 0.238057228 0.5 0.454 1 Brcc3 0.111565681 0.20572452 0.276 0.218 1 Tspan9 0.112025748 0.211703014 0.115 0.069 1 Snrnp200 0.115532314 0.217488694 0.264 0.195 1 Fech 0.1178627 0.212953066 0.557 0.489 1 Slc4a4 0.11806357 0.20735045 0.414 0.339 1 Eif3g 0.119048105 0.200216768 0.385 0.322 1 Gpr146 0.120071427 −0.251942829 0.293 0.351 1 Cnih1 0.125250208 0.219317444 0.368 0.316 1 Actr3 0.12982029 0.20860417 0.287 0.236 1 Ppm1k 0.129962879 0.324630558 0.511 0.483 1 Ablim3 0.135177431 −0.223008512 0.086 0.132 1 Cast 0.139729608 0.261775559 0.339 0.276 1 Papola 0.142115112 0.225706284 0.471 0.425 1 Slco1b2 0.143447728 −0.212121676 0.874 0.908 1 Pctp 0.150651256 −0.207440425 0.293 0.345 1 Rps15a 0.153126618 0.245141756 0.351 0.293 1 Nckap1 0.160335985 0.210159632 0.397 0.345 1 Plekha8 0.165399995 0.226910035 0.201 0.149 1 Pbrm1 0.165692031 0.200710098 0.351 0.293 1 Pgm3 0.177901845 0.20414768 0.241 0.184 1 D8Ertd738e 0.203182332 0.241338629 0.466 0.425 1 Fyttd1 0.241823018 0.207298863 0.305 0.247 1 Tbl1xr1 0.260541136 0.233716463 0.299 0.253 1 Btg2 0.269475652 0.213428173 0.362 0.328 1 Apoa4 0.29179639 0.238743063 0.563 0.546 1 Actn4 0.315895266 0.223722393 0.489 0.46 1 Gcc2 0.316131341 0.217374612 0.236 0.195 1 Larp4b 0.338255167 0.205260189 0.368 0.345 1 Ptcd2 0.391938515 0.247969764 0.207 0.172 1 n-R5-8s1 0.400728491 0.233544882 0.523 0.506 1 Pcyt1a 0.423598847 0.275819635 0.374 0.339 1 Mettl16 0.458903759 0.204651364 0.201 0.172 1 Mgea5 0.499176875 0.213978639 0.339 0.322 1 Gm26917 0.514428432 −0.298541162 0.293 0.328 1 Marf1 0.515620318 0.236482432 0.213 0.195 1 Wdr3 0.682566958 0.204292215 0.155 0.144 1 Map3k12 0.755668288 −0.225875211 0.029 0.034 1 Cyp2a5 0.771556335 0.324941979 0.316 0.328 1 Pdpk1 0.934116563 −0.229596112 0.213 0.213 1

To identify pathways and potential upstream regulators involved in cell cycle activation, Applicants performed GSA over DEG calculated between CCs and NCs from A24 and P48, revealing an upregulation of cell cycle-related pathways. Further, there was a strong enrichment for Wnt-related pathways (FIG. 29 ). It has been shown extensively that Wnt signaling is involved with normal hepatocyte turnover and liver regeneration^(10,12,21-24,13-20) These Wnt factors are thought to be derived from the endothelium and contribute to the activation of hepatic progenitor cell genes (Axin2, Tbx3, and Sox9)^(12,30). Applicants observed up-regulation of Axin2, Tbx3, and Sox9 in each acute injury model, with expression reaching multiple cell layers into the midzone FIG. 30 ). These data support activation of WNT/-catenin signaling in response to injury, which may be co-localized with the induction of genes associated with hepatic plasticity^(12,30). This could explain the observation that hepatocytes outside of a particular zone have the ability to activate the expression of genes that may be lost due to zone-specific injury (APAP) or extreme tissue loss (PH), such as midzonal hepatocytes up-regulating Glu1 in either injury model.

Wnt Signaling Mediates Functional Compensation in Addition to Proliferative Response

Given the demonstrated role of Wnt signaling in establishing liver zonation and proliferation during liver regeneration, Applicants investigated whether Wnt signaling might activate adaptation of already present hepatocytes to maintain essential hepatic function^(13,31-34). scRNA-seq data corroborated previous observations of increased Wnt activity in proliferating hepatocytes (FIG. 22A)^(17,34,35). Further, it revealed activation of Wnt target gene expression in the majority of hepatocytes in both the APAP and PH models, preceding the onset of cell proliferative activity (A6 and P3, FIG. 22B).

To identify if hepatic compensatory response following injury is also contributed by Wntβ-catenin signaling, Applicants evaluated hepatic gene expression via smFISH in hepatocyte-specific β-catenin KO mice after PH (FIG. 31 ). Functional compensation was β-catenin-dependent for select genes, such as Alb and Glu1. To identify the cellular source for secreted Wnt ligands responsible for functional compensation dependent on Wnt/β-catenin signaling, Applicants examined the contribution of both endothelium- and macrophage-derived Wnts using conditional Wntless (Wls) KO alleles that have intact β-catenin but lack proper Wnt processing and Wnt secretion from the respective cell populations (FIG. 22C)^(13,36). Loss of either endothelium- or macrophage-derived Wnts, resulted in a down-regulation of hepatic function genes at baseline consistent with the role of Wnt signaling in the establishment and maintenance of hepatic gene expression during quiescence^(34,37,38) (FIG. 22D, 22E). Importantly, EC-Wls-KO mice are still able to transcriptionally compensate following PH. In contrast, loss of Wnt processing in macrophages of Mac-Wls-KO mice resulted in down-regulation of all examined hepatocyte genes in response to injury with the complete inability for transcriptional compensation (FIG. 22D). No change in resident hepatic macrophage numbers was observed (FIG. 32 ). Taken together, these data reveal that macrophage-derived Wnts are required for the observed functional compensation identified in this study, while endothelium-derived Wnts play a less significant role in this response.

Discussion

The liver uniquely maintains complex metabolic function throughout injury and subsequent regeneration to enable survival of an organism^(39,40). It has long been thought that the liver has sufficient functional reserve to maintain these functions through excess baseline capacity″, but the exact hepatic reserve capacity has been mostly a theoretical concept. Liver injury induces a regenerative response where functionally active hepatocytes are the major contributor to cellular regeneration. Turnover of hepatocytes in the uninjured organ is rather slow, with the entire liver being repopulated by new hepatocytes after ˜1 year^(12,45). The liver can quickly respond to an acute insult, however, through activation of a regenerative response. Liver regeneration within the mouse model shows a peak of hepatocyte proliferation between 30-36 hrs for both PH and APAP-induced injury^(46,47). Cell cycle genes are activated well before hepatocyte proliferation begins (priming phase) following injury^(39,40,48). However, cell cycle inhibitors, such as p21 and p27, are concurrently up-regulated early in liver regeneration and block progression of hepatocytes into the cell cycle^(49,50). It has been speculated that this co-expression of both stimulators and repressors of the cell cycle aides in the control of liver regeneration to a precise end point³⁹.

Here, Applicants describe a mechanism by which the liver has the ability to maintain essential liver function through transcriptional compensation when the proliferative response is delayed. Hepatocytes upregulate transcription of important liver genes, typically by adapting expression patterns extending beyond zonal boundaries. Importantly, many hepatocyte function genes are expressed predominantly in non-proliferating hepatocytes, while those cells that enter cell cycle by expression profile express hepatocyte function genes at lower levels. Collectively, our data define a novel compensatory phase following liver injury, thereby complementing previous studies which have elegantly established the field of liver regeneration by focusing on the hepatic proliferative response.

In addition, Applicants define a novel dual role for Wntβ-catenin signaling in liver regeneration: it not only promotes cell proliferation and cellular recovery, as shown in multiple studies^(10,12,21-24,13-20,) but it is also indispensable for functional compensation to maintain essential liver functions (FIG. 23 ). Applicants identified macrophages, but not endothelial cells, as a key source of secreted Wnts that enable transcriptional compensation. This is in contrast to other studies which have highlighted the contributions of endothelial-derived Wnts to maintenance of hepatic zonation as well as both endothelial and macrophage secreted Wnts to cellular proliferation^(13,23,37,38). Applicants postulate that macrophages, which are responsible for broad inflammatory and immunologic functions⁵¹, are also essential for delivering Wnts locally throughout the entirety of the hepatic lobule (midzone and periportal areas) because of their ability to migrate and release Wnt ligands throughout the tissue. Our findings further highlight the potential of the Wnt/β-catenin pathway as a therapeutic target in acute liver failure and other liver pathologies, where maintenance of liver function is essential. Future studies will be needed to identify specific Wnt ligands to promote liver function, regeneration, and survival in regard to multiple pathologies that result in acute liver failure.

Methods Animals

Three-month-old, male, C57BL/6J mice, purchased from Jackson Laboratories (Bar Harbor, Me., USA), were used in acute liver injury studies (APAP and PH). -catenin KO studies were conducted using Alb-cre^(+/−); Ctnnb1^(flox/flox) mice. Wntless KO studies were conducted using Lyve1-cre^(+/−); Wls^(flox/flox) (endothelial cell, EC-Wls) and Lyz2-cre^(+/−); Wls^(flox/flox) (macrophages, Mac-Wls). All animals were housed in Association for Assessment and Accreditation of Laboratory Animal Care—accredited facilities at Brigham and Women's Hospital (Boston, Mass.) under a standard 12-hour light/dark cycle with access to chow and water ad libitum. The Institutional Animal Care and Use Committee at Brigham and Women's Hospital approved all studies.

Acetaminophen (APAP) Exposure

Mice were fasted 12 hours before administration of APAP. APAP was dissolved in warm 0.9% saline, and mice were injected with 300 mg/kg APAP, i.p. Food was returned to the mice after APAP treatment. Mice were then used for isolation of primary hepatic cells for single cell RNA-sequencing or tissue harvest for further downstream analysis.

Partial Hepatectomy

Partial hepatectomy surgeries were performed as previously described⁵². Mice were euthanized at 3 hrs, 48 hrs, and 5 days post-partial hepatectomy by cervical dislocation under isoflurane anesthesia and livers were harvested for downstream analysis. Further, mice were used for isolation of primary hepatic cells at 3 hrs, 48 hrs, and 5 days post-partial hepatectomy.

Isolation of Primary Hepatocytes and Non-Parenchymal Cells

Mouse hepatic cells were isolated by a modification of the two-step collagenase perfusion method⁵³. Cells were isolated from untreated (n=3 for each sex), APAP-treated mice (n=2 for each sex at 6, 24, 48, and 96 hours following APAP exposure), and mice subjected to partial hepatectomy (n=3; 3 hrs, 48 hrs, and 5 days). The digestion step was performed using Liver Digest Medium (Cat. #17703034; ThermoFisher Scientific; Pittsburgh, Pa., USA). Cell suspensions were used immediately for Seq-Well.

Tissue Harvest

Untreated (n=3 for each sex) and APAP-treated mice (n=3 for 6, 24, 48, and 96 hours following APAP exposure and 3, 48, and 120 hours following PH) were euthanized by cervical dislocation following carbon dioxide exposure. A portion of liver tissue was fixed in 10% neutral buffered formalin for 48 hrs and further processed to obtain paraffin blocks and 5 μm thick sections. A portion of liver tissue was frozen in optimal cutting temperature (OCT) medium and used to obtain 10 μm fresh frozen sections.

Library Preparation and Sequencing

Sequencing libraries were prepared from the single-cell suspension using the Seq-Well method as described in Gierahn et. al. 2017. Briefly, a microwell array was loaded with barcoded polyT mRNA capture beads (Chemgenes). Then 200 μl of media containing 15,000 single cells was loaded onto the array and allowed to settle into the wells by gravity. Membrane sealing, lysis, hybridization, reverse transcription, exonuclease digestion, second strand synthesis, PCR, and library construction by Nextera were all performed as previously described⁵⁴. Resulting libraries were quantified by Qubit and tape station (Agilent), and sequenced on an Illumina NextSeq 500 (UT and APAP samples, 2 arrays per run) or a NovaSeq (PH samples, 10 arrays per run) 30 cycle, paired end sequence reads, single 8 cycle index for NextSeq or dual 8 cycle indexes for NovaSeq.

Single-Cell Sequencing Data Processing

Sequencing data was demultiplexed and aligned to mm10 with STAR aligner. Libraries were sequenced to an average depth of >48,000 reads per cell per sample. See Table 12 for additional sequencing and data quality metrics.

Barcodes with fewer than 400 genes were discarded from the genes x cells data matrix as non-cells, with 16,019 cells remaining. Data was log normalized and TPM-like (base 10,000) normalized and analyzed using the Seurat package in R⁵⁴. The resulting data displayed fairly even nGene and nUMI distributions across each sample type (FIG. 24H). Applicants performed a principal component analysis (PCA) and selected the top 13 principal components (PCs) for tSNE dimensional reduction. Applicants then performed shared nearest neighbors (SNN) clustering, and identified 14 distinct clusters in the data (FIG. 24C, 24D). Applicants calculated differential expression across the clusters using Wilcox test in the FindAllMarkers function in the Seurat R package and quantified expression of marker genes for known liver cell populations (FIG. 24D, 24E). Applicants identified nine high-quality hepatocyte clusters, separated by treatment condition; one low quality hepatocyte cluster with a high percent mitochondrial content and low nGene and nUMI; a kupffer cell cluster; a liver endothelial cell (LEC) cluster; a neutrophil cluster; and a mixed immune cluster, which appears to contain T cells, B cells and monocytes. Applicants calculated a hepatocyte signature score using AddModuleScore in Seurat over multiple highly expressed hepatocyte genes which span the lobule: Apoa1, Glu1, Acly, Asl, Cyp2e1, Cyp2f2, Ass1, Alb, Mup3, Pck1, G6pc, Fabp1.

In order to focus on hepatocyte responses, Applicants subsetted our data to include on the nine high-quality hepatocyte clusters. Following subsetting, Applicants observed a remaining few cells scoring low on the hepatocyte signature. Applicants filtered out any cells with a Hepatocyte Signature score less than 3 standard deviations below the average as non-hepatocytes (FIG. 24E). These non-hepatocyte cells originated primarily from the A6 sample, which dhad the largest immune infiltration in response to injury and the highest fraction on non-parenchymal cells in the total sample. The filtered non-hepatocytes are likely non-parenchymal cells incorrectly assigned to a hepatocyte cluster by SNN. Following these filtering steps, Applicants retained 10,833 high-quality hepatocytes for analysis.

Single-Cell Sequencing Data Analysis (Hepatocyte Data)

Applicants performed dimensional reduction and clustering again on our filtered hepatocyte only dataset. Principal component 1 (PC1) describes 46.9% of and captures technical variation (nGene, nUMI) in the data (FIG. 25E). This is not surprising for a dataset comprised of a single cell type. Each of our treatment conditions scores similarly on PC1 (FIG. 25B). PC2 partly captures pericentral-periportal variation. Applicants identified zonally restricted genes in PC2 loadings (Cyp2e1, Cyp1a2, Gtsm3; Cyp2f2). Applicants also noted periportal-pericentral variation captured in PC4.

To more clearly visualize pericentral-periportal variation, Applicants scored cells on this pericentral periportal metric. To generate a list of pericentral genes, Applicants calculated gene-by-gene correlations with Cyp2e1, a canonical pericentral gene. To generate a pericentral gene list, Applicants selected genes positively correlated with Cyp2e1, and to generate a periportal gene list, Applicants selected genes negatively correlated with Cyp2e1 (Table 17). To generate a list of genes to be used for our signatures, Applicants considered all genes with a Cyp2e1 correlation >0.3 for PCHSig and a Cyp2e1 correlation <−0.3 for PPHSig. From the genes falling within this range of values, Applicants selected moderately expressed genes with large variability in expression across the dataset, removing lowly expressed genes and genes expressed in small numbers of cells. Positive correlations with Cyp2e1 range from 0.823 (Cyp2c29) to 0.356 (Ang); negative correlations with Cyp2e1 range from −0.569 (Cyp2f2) to −0.311 (Serpina12). The 0.3/−0.3 cutoff is more than 3 standard deviations above/below the mean of all gene correlations with Cyp2e1 (mean=−0.01280654; mean+3sd=0.2605311; mean−3sd=−0.2861442). Applicants then calculated the pericental hepatocyte (PCH) score and periportal hepatocyte (PPH) score using AddModuleScore for these genes. Applicants then confirmed that PCH Score and PPH Score are inversely correlated as expected. Applicants observe a pericental-periportal gradient across PC2 using these scores (FIG. 25A-25H). To generate a single score that captures pericentral-periportal character, Applicants subtracted the PCH Score from the PPH Score to create the PPH-PCH Score, in which pericentral hepatocytes will score negatively and periportal hepatocytes will score positively.

TABLE 17 Gene signatures used to define pericentral hepatocytes (PCH) and periporatal hepatocytes (PPH). PCH genes PPH genes Lect2 Hal Rnase4 Etnppl Ang Sds Oat Hsd17b13 Gulo Serpina12 Cyp2c29 Hsd17b13 Cyp2e1 Gas Cyp2c50 Aqp8 Cyp2a5 Cyp2f2 Cyp2c37 Aldh3a2

To better visualize the data, Applicants performed tSNE dimensional reduction. Hepatocytes from all samples look rather similar in lower PCs which describe shared variation, such as technical differences or cross-lobule variation, while the higher PCs capture inter-sample variation. Applicants calculated percent variation captured per PC and generated an elbow plot to determine the correct number of PCs to use in further analysis. Applicants selected the top 13 PCs to include in our analysis, which well separated samples by treatment condition and did not appear to be driven by technical artifacts. Applicants observe a technical gradient across each cluster (which is orthogonal to the pericentral-periportal gradient across each cluster), but the clusters themselves do not appear technically driven (FIG. 25H).

Heatmap genes were found using FindAllMarkers in Seurat, Wilcox test, min.percent=0.10, thresh.use=0.25. Mitochondrial and hemoglobin genes were removed from the list prior to heatmap plotting.

Shared and unique by injury model gene lists were assembled by combining DE results across all time points for each injury. Applicants ran differential expression using Wilcox test in the FindAllMarkers Seurat function between each treatment condition (A6, A24, A48, A96, PH3, PH48, PH120) individually and untreated (UT). Applicants then combined results across all time points within each injury model to obtain a list of all differentially expressed genes from any time point in APAP experiments (A6, A24, A48, A96) and PH (PH3, PH48, PH120). A small number of genes were up at one time point, but down at another. In these cases, the gene was retained in the list (up- or down-regulated) with the largest magnitude average log fold-change to capture to more significant change in expression.

Applicants ran pathway analysis on the composite DE results using the piano R package. Reference gene sets were downloaded from MSigDB (Broad Institute). Applicants used geneSetStat=“fisher”, adjMethod=“fdr”, and signifMethod=“geneSampling”. Applicants then parsed the results to identify shared and unique reference gene sets for each injury. Any reference gene set with a q-value greater than 0.05 was discarded as insignificant. Applicants then identified reference gene sets with significant overlaps with only APAP and with only PH composite DE results. To focus on truly unique responses, Applicants filtered out any reference gene set from the unique tables which had a q-value <0.2 for the other injury model. Applicants then identified shared responses by compiling all reference gene sets with a q-value of <0.05 in both APAP and PH. Selected reference gene set −log(q) are plotted in FIG. 20 .

To identify cycling cells in the data, Applicants calculated Cell Cycle Score using AddModuleScore in Seurat over the cell cycle markers found in Tirosh et. al. 2015. Applicants classified cells with a Cell Cycle Score 2 standard deviations above the average as cycling cells (FIG. 4 ). To better compare cycling and non-cycling cells (CC and NC, respectively), Applicants subsetted the data to create a dataset containing all 51 CCs from the A24 condition and an equal number of NCs also from A24; similarly, Applicants created a dataset containing all 123 CC from PH48 and an equal number of NCs also from PH48. Pathway analysis was done on a DE result obtained from comparing 174 CC from A24 and PH48 against an equal number of NCs from these time points. Piano was run as described above. FIG. 21 plots −log(q) values for selected reference gene sets with a q value <0.05. Wnt Target Labbe Sig was calculated using AddModuleScore and the reference gene set LABBE_WNT3A_TARGETS_UP which was identified as significant in Piano gene set enrichment analysis.

Immunohistochemical Analysis

Histology was performed by the histology core at Beth Israel Deaconess Medical Center using standard procedures and automated workflow. Samples were processed and embedded following fixation in 10% neutral buffered formalin for 48 hrs. Samples were embedded in paraffin and sectioned at 5 m thick. Immunohistochemistry was performed on a Leica autostainer (Leica Biosystems) with enzyme treatment (1:1000) using standard protocols. The antibody used for assessment of cell proliferation was PCNA (Cell Signaling, Cat. 13110, 1:800), and cell death was ApopTag Peroxidase In Situ Apoptosis Detection Kit (Millipore, Cat. #S7100). Macrophages were stained using the anti-F4/80 (Cell Signaling, Cat. 70076, 1:500). Sections were then counterstained with hematoxylin, dehydrated, and film cover slipped. Four representative images were captured per slide. TUNEL-positive area, PCNA-positive cells, and F4/80-positive cells were measured and averaged across the four images for each sample using Fiji.

Single Molecule Fluorescent In Situ Hybridization (smFISH)

smFISH was conducted using RNAscope technology (RNAscope Fluorescent Multiplex Kit; Cat. #320850; Advanced Cell Diagnostics; Neward, Calif., USA). Fresh frozen sections (10 m thick) were used following the manufacturer's guidelines. Probe sets were designed by the manufacturer and can be found at acdbio.com/catalog-probes. A 6×6 40× field was captured of a 10 μM z-stack (0.5 uM per slice). This resulted in multiple liver lobules available for analysis within a single section. Images were cropped to the size of a single liver lobule and cellular outlines were defined using CellProfiler⁵⁵. smFISH signal was then quantified using FISH-quant⁵⁶. Post-processing of mRNA detection was performed with custom-written Python scripts (available at bitbucket.org/muellerflorian/pyfishquant/). Pseudo-color images of transcript abundance were generated by setting the pixel values of each segmented cells to its corresponding transcript level. To determine the spatial expression gradients relatively to the central vein, Applicants manually outlined the vein as a polygon. This polygon served as a reference point to count RNAs in concentric rings. These counts were lastly renormalized by the ring area contained within the image.

Statistical Analysis

Applicants calculated P values for shifts in gene expression or module scores using the Wilcox test, Bonferroni corrected for multiple testing. Gene set enrichment results in piano were calculated using Fisher's test and the gene sampling method and corrected by FDR. P values for average RNA expression (smFISH) and IHC counts (PCNA, F4/80, and TUNEL) were calculated using Welch's ANOVA tests.

The following includes references pertinent to example 3.

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Example 4—High Fat Diet scRNA-Seq Captures Many Cell Types Across Tissues

To profile cellular responses to pro-obesity HFD, Applicants performed Seq-Well on mice maintained on a HFD (60% of calories from fat) as described in Beyaz et. al.¹ for six months. Diet-induced cellular changes are likely in progress by six months, with mice progressing to more severe manifestations of obesity-associated metabolic changes and gastrointestinal disease by around nine to 14 months. Obesity is linked to cancer and inflammation in both the gut and liver; therefore, Applicants profiled samples from multiple gastrointestinal and complementary immune sites to gain a fuller picture of the effects of HFD spanning multiple organs.

Samples from peripheral blood (PB), bone marrow (BM), spleen (Sp), liver hepatocyte-enriched (Hep), liver non-parenchymal-enriched (NPC), proximal small intestine (Prox), distal small intestine (Dis) and Colon (Col) were processed to single cell suspension and loaded onto a Seq-well array (Table 18, Methods). Prior to loading, crypts from proximal small intestine, distal small intestine and colon were isolated, dissociated into a single cell suspension and sorted into CD45+ and EPCAM+ populations to enrich for immune cells in the sample. The sorted populations (20,000 EPCAM+, 5,000 CD45+) were mixed together and loaded onto an array. Libraries were then prepared and sequenced on a Nova-Seq.

TABLE 18 nGene nUMI nCell filter CD2Col 2212 4889 1737 CD2Dis 2250 6129 1332 CD2Hep 2531 15127 1328 CD2NPC 670 2639 1326 CD2PB 453 1019 449 CD2Prox 4090 13068 1756 CD4BM 3406 10330 1868 CD4Col 2997 9707 1241 CD4Dis 3740 11319 1607 CD4Hep 239 1786 335 CD4NPC 464 1878 742 CD4PB 1755 5002 1075 CO4Prox 3693 10280 1965 CD4Sp 2870 7767 1543 HF2Col 2435 8610 935 HF2Dis 3309 10264 1292 HF2Hep 681 4713 964 HF2NPC 786 2763 1371 HF2PB 1409 5685 878 HF2Prox 2471 8137 1170 HF3BM 1757 4275 1804 HF3Col 646 1917 608 HF3Dis 1251 2748 1279 HF3Hep 216 837 231 HF3NPC 189 899 342 HF3PB 675 1393 745 HF3Prox 2749 6316 1813 HF4Col 3455 9932 1296 HF4Dis 3551 9690 1961 HF4Hep 540 1700 1347 HF4NPC 458 1696 960 HF4PB 1973 4497 1622 HF4Prox 3416 8702 1683

Following data processing and filtering, Applicants obtained a total of 42,684 cells. To visualize the data, Applicants performed dimensional reduction by Principal Components Analysis (PCA) and t-Stochastic Neighbor Embedding (t-SNE). Applicants identified groups of similar cells using Shared Nearest Neighbor (SNN) clustering, and generated module scores from marker genes highly expressed in various cell types to identify the cell type present in each cluster (FIG. 33A-33D, Methods). Applicants identified several clusters and multiple types of intestinal cells: stem/transamplifying (STA), Enterocyte, Enteroendocrine (EEC), Goblet, Paneth and Tuft. STA and Enterocyte clusters separate mainly by point of origin: proximal, distal, or colon (FIG. 33A-33D). Applicants observe immune cell (B cell, T cell) clusters populated by cells from many different compartments. Liver-resident Kupffer and hepatocyte clusters emerge, with clear separation by diet condition in hepatocytes. Finally, Applicants identified bone marrow- and spleen-specific clusters of immature immune cells.

Table 18 provides samples processed from two control diet (CD2, CD4) and three high fat diet (HF2, HF3, HF4) mice. Samples were prepared from bone marrow (BM), colon (Col), distal small intestine (Dis), liver hepatocyte-enriched (Hep), liver NPC-enriched (NPC), peripheral blood (PB), proximal small intestine (Prox) and spleen (Sp). Due to technical challenges not all samples were obtained from all mice. Number of genes (nGene) and number of unique molecular identifiers (nUMIs) were calculated for each sample over all events called in alignment. Number of cells remaining after filtering for >500 transcripts and >200 genes (nCell filter) reported for each sample.

Applicants applied quality metrics: number of genes (nGene), number of unique molecular identifiers (nUMI, number of RNA molecules captured) and percent mitochondrial content (percent.mito; NB high mitochondrial content can indicate cell membrane disruption from excessively harsh processing and diminished data quality); and Applicants identified two low quality clusters mainly originating from colon and from liver which Applicants omit from further analysis (FIG. 33C, 33D). Applicants noted lower quality in the HFD hepatocyte clusters relative to other cell types. Cells isolated from the livers of HFD animals are incredibly delicate, likely due to increased volume of fats, and strongly encapsulated within the more fibrotic tissue found in HFD. This increased tissue fibrosis and larger gross liver size necessitated harsher profusion and digestion conditions, as well as longer treatment time to liberate single cells for analysis. It has also been noted in the literature that hepatocyte mitochondrial content can be very high and that hepatocytes appear highly susceptible to damage from processing. It has been postulated that these large fragile cells' membranes are more easily disrupted which may further inflate mitochondrial content due to loss of cytosolic mRNAs. Here, metabolic changes induced by HFD may also contribute to shifts in mitochondrial gene expression.

HFD-Induced Changes in the Gut

To more clearly assess diet-induced shifts in the gut, Applicants subsetted the dataset to include only samples that originated in the proximal, distal or colonic regions, and filtered out the low-quality colon cluster and the irreproducible HF2 Proximal cluster (Methods). Applicants performed dimensional reduction and SNN clustering again on this subsetted data, and assigned cell type identities to each cluster as Applicants did for the full dataset. Each cluster is populated with cells from HFD and CD mice, yet Applicants noticed some diet-based variation within clusters, especially in the enterocyte clusters (FIG. 34A, 34B).

Previous work has reported that PPAR signaling drives differences between HFD and CD intestinal cells at 9-14 months on the diet. Applicants calculated a PPAR signaling score over the gut cells to determine whether this pathway is already activated in the intestines at 6 months on HFD in each of the cell type clusters captured (Methods). Indeed, in some of the cell type clusters Applicants observe upregulation of PPAR target genes (KEGG_PPAR_SIGNALING_PATHWAY, Broad MSigDB) in the HFD compared to the CD condition, as previously reported¹ (FIG. 34C). Interestingly, Applicants found the strongest upregulation of the PPAR program in the proximal enterocyte cells (d=2.13), upregulation in the proximal stem (d=1.94) and transamplifying cells (d=1.94), and little to no upregulation in the distal and colon samples as well as for cell types other than enterocyte/transamplifying/stem (d=0.629 to 0.03) (FIG. 34C). These patterns are represented in each of the multiple mice in this dataset (data not shown). This supports the report by Beyaz and colleagues of an HFD-induced increase in PPAR target gene expression in the small intestine and colon at around one year on HFD¹. the data show significant upregulation of PPAR targets has begun by six months on HFD in the proximal region, but suggests that changes in the distal or colonic regions may involve lower levels of PPAR activation, occur more slowly, or involve pathways other than PPAR at this time point.

To explore other pathways which may be involved in the distal small intestine and colon Applicants performed pathway analysis with Ingenuity Pathway Analysis (IPA) from Qiagen. Applicants found decreased activity of RB1, a tumor suppressor, in HFD enterocytes from the proximal region (z-score −2.945, p-value 5.51e-03) and stem/transamplifying cells from the colon (z-score −3.537, p-value 1.41e-11). Applicants also found upregulation of RELA, involved in NF-κB signaling and inflammation in colon stem/transamplifying HFD (z-score 2.779, p-value 1.85e-05).

Next, the gut immune cell cluster was subsetted to further refine the cell type cluster assignments by iterative clustering. Applicants identified several cell types, including B cells (naïve/memory and plasmablast) CD4+T cells, CD8+T cells/NK cells, dendritic cells (DC), macrophages and neutrophils, and noticed fluctuations in the frequencies of these subsets between HFD and CD (FIG. 34D). Importantly, each of the gut samples was sorted prior to loading onto the Seq-Well array to enrich for immune cells, and each array was loaded with the same 1:4 ratio of CD45+ to EPCAM+ cells (Methods). However, Applicants ultimately obtained inconsistent numbers of immune cells in each of the samples. This is likely due to a combination of variable relative viability among cell types and sequencing depth. The absolute number of immune cells is variable, and the ratio of immune to non-immune ranges from 14% immune in HF2 to 2% in HF4. There appears to be a trend of more deeply sequenced samples (CD2, HF2) containing more immune cells, suggesting deeper sequencing of samples from experiments 3 and 4 may increase immune cell numbers. The immune cells that make up the immune component in each sample vary considerably in their fractional abundance of immune cell types between HF and CD. The HFD samples have a much higher fraction of B cells while the CD immune population contains more T cells, dendritic cells, and macrophages. This variability may represent an infiltration of B cells or efflux of T cells and macrophages in HFD, or the reverse in CD. Since the protocol accepts a set number of cells an input, an increased infiltration of one cell type will result in a decrease in the fractional abundance of others in the data, making absolute abundance difficult to determine the data suggests some shift in immune composition, but additional experiments, such as flow analysis, are needed to quantitatively ascertain the abundance of various immune subsets in HFD and CD guts.

HFD-Induced Changes in the Liver

Obesity is known to increase risk for both intestinal and liver disease. The HFD mice in this study do begin to develop liver problems by 6 months on the diet and, in some cases, progress to spontaneous HCC at later time points. To dissect and study HFD-induced transformations in the liver at single-cell resolution, Applicants applied Seq-well to liver samples from HFD and CD. Biological changes in the HFD liver make hepatocytes more sensitive to processing due to fat accumulation while, at the same time, making the liver larger, more fibrotic and difficult to dissociate, presenting challenges in processing. For these reasons, the HFD liver data is of lower quality (lower nGene, lower cell number, higher percent mitochondrial content) than CD liver, but still interpretable (Table 18, FIG. 35A). Applicants have already made several adjustments to the protocol to improve data to this point (Methods), but future iterations may make additional adjustments to improve HFD liver data quality.

Applicants subsetted the dataset to include only samples originating in the liver, performed dimensional reduction and reclustering (Methods). Applicants identified expected liver cell types: Hepatocytes, liver endothelial cells (LECs), Kupffer cells, macrophage/monocytes, pDCs, T cells, B cells and neutrophils (FIG. 35A, 35B). Intriguingly, the hepatocytes form distinct clusters separating by diet, with some diet-based shifts evident in other cell types as well (FIG. 35C).

Applicants performed iterative clustering over the non-parenchymal cells of the liver to gain greater resolution in calling the cell types represented. Applicants identified Kupffer cells, liver capsule macrophages (LCMP), pDCs, Neutrophils, liver endothelial cells (LEC), B cells, and T cells (FIG. 35D). Kupffer cells were the most plentiful cell type in the NPC dataset and appear to separate slightly by diet condition (FIG. 35E). Applicants ran IPA over genes differentially expressed between HFD and CD Kupffer cells. Within “Diseases & Functions”, Applicants found upregulation in HFD of “Immune response of macrophages” (z-score 1.778, p-value 1.65e-11), “Activation of cells” (z-score 2.294, p-value 2.42e-42) and “Wound” (z-score 2.219, p-value 1.97e-08). HFD also showed upregulation of the activity of several upstream regulators such as pro-inflammatory NF-κB (z-score 2.179, p-value 3.98e-11) and TREM1 (z-score 2.938, p-value 2.31e-07). Taken together, these results present HFD kupffer cells as more activated and more inflammatory than in CD (FIG. 35F).

To specifically analyze cellular responses in the hepatocyte data, Applicants selected hepatocyte clusters, filtered on a mitochondrial content cutoff of 50%, as has been reported previously¹⁸, and performed iterative clustering over the remaining cells (Methods). Applicants identified a large cluster of hepatocytes originating mainly from CD2, a large cluster from HF4 and HF3, a smaller cluster from HF2, a small cluster from CD4 and another small cluster from HF2 (FIG. 35G). Applicants performed differential expression between the HFD and CD hepatocytes and ran pathway analysis on the resulting differentially expressed genes through IPA. Results from IPA “Diseases & Functions” identifies upregulation of “Liver steatosis” (z-score 3.522, p-value 2.93e-21), “Hepatic steatosis” (z-score 3.522, p-value 2.93e-21), “Inflammation of liver” (z-score 1.857, p-value 1.50e-09), Oxidative stress (z-score 3.657, p-value 1.10e-11) and “Accumulation of cholesterol” (z-score 2.320, p-value 3.95e-07), as well as a decrease in “Synthesis of lipid” (z-score −3.501, p-value 6.89e-36) in the HFD compared to CD hepatocytes. IPA upstream regulators show a downregulation in HFD of activity of SREPF2 (also known as Srebp2, z-score −4.883, p-value 1.67e-24), a transcription factor responsible for activating synthesis and uptake of cholesterol and fatty acids. This aligns well with the expected biology of the HFD liver, confirming that Applicants have captured interpretable data.

Next, Applicants asked whether activation of the PPAR pathway in the HFD condition occurs in the liver as it does in the gut. Applicants found PPAR target genes upregulated in HF2 compared to CD2, but down regulation of PPAR in HF3 and HF4 compared to CD2 (FIG. 35H). Samples from experiment 2 were resequenced to achieve greater sequencing depth, while some samples from experiments 3 and 4, especially HF4Hep, are undersequenced, possibly affecting PPAR target gene expression sensitivity. Applicants will address this possibility by resequencing these samples to improve depth. Alternatively, PPAR activation may occur in some HFD mice, but not others at the six-month time point. In search of other regulators which may contribute to HFD-induced changes in the liver, Applicants combed the Upstream Regulator IPA results for potential drivers of HFD-induced changes in the liver. IPA identifies significant downregulation in HFD of activity of RB1 (z-score −5.82, p-value 8.43e-14), a transcription factor with tumor suppressive function²¹, and down regulation, particularly in HF4, of activity of CEBPA (z-score −4.749, p-value 4.93e-13), a transcription factor involved in cell cycle regulation, lipid and glucose metabolism in the liver, and leptin expression and body weight homeostasis, whose function is known to be suppressed in HCC and other types of liver disease (FIG. 35I). IPA also identified upstream regulators whose function increased under HFD conditions, including NCOR1 (z-score 2.6, p-value 2.85e-10), which can contribute to thyroid hormone resistance, and hormonal and metabolic changes. Additional work is needed to further explore and validate the potential contributions of these pathways to HFD-induced changes in the liver.

Changes in proliferative potential and “sternness” can prime cells to grow in dysregulated ways, possibly leading to cancer. Although a dedicated liver stem cell population has never been definitively identified¹², Applicants postulate that a subset of hepatocytes may activate stem function in response to HFD and progress toward the development of HCC. Thus, Applicants scored hepatocytes on a stem cell signature to identify changes is stem-like expression and searched for changes in these stem-like cells which may lead to HCC. More specifically, Applicants scored hepatocytes on expression of stem marker genes Lgr5, Axing, Sox9, Asc12, Tbx3 and Gkn3 (Methods). Applicants identified hepatocytes which have activated a stem cell program as cells scoring at least two standard deviations above average. (FIG. 36A). A much higher percentage of HFD hepatocytes score as stem cells than CD hepatocytes (5.6% vs 0.92%), supporting the notion that HFD may increase stemness in the liver, similarly to what has been reported in the gut. High expression of the stem signature in hepatocytes was driven mainly by expression of Sox9, Lgr5 and/or Axin2. HFD appears to dysregulate expression of these genes, with suppressed expression of the stem gene Sox9 and increased expression of Lgr5 and Axin2 in HFD compared to CD (FIG. 36B). Interestingly, Lrg5 and Axin2, the stem genes most highly expressed in HFD hepatocyte stem cells, are expressed largely mutually exclusively, in contrast to the gut where they are coexpressed (FIG. 36C). Many of the genes correlated with Lgr5 expression and Axin2 expression in the hepatocyte dataset are involved in cytokinesis and cell cycle pathways, supporting the notion that cells expressing these genes may possess increased proliferative potential. Further identification and characterization of changes in stemness within hepatocytes will serve to pinpoint the cellular origins of HCC, which remain poorly defined.

Liver Organoids

Organoids can serve as a useful model system for evaluating perturbations in vitro and assessing the stemness of input samples. In the intestine, HFD samples possessed greater capacity to form and grow organoids, a characteristic of their enhanced stemness. This same characteristic may enhance their ability to progress to tumors. Here, Applicants pilot a recently published hepatocyte organoid protocol with the HFD and CD hepatocyte-enriched samples to assess their relative abilities to form and grow organoids.

Applicants seeded organoids in matrigel and noted clear morphological differences between the HFD and CD hepatocytes, suggestive of their biology. Despite efforts to seed equal numbers of cells for both conditions, in this pilot experiment, the HFD was seeded much less efficiently than the CD (more cells matrigel at day 0 for CD than HFD) (FIG. 37A). As expected, only a few organoids formed and grew very slowly. Applicants continued to grow the organoids under the prescribed conditions and noted heterogeneous morphology. Some organoids appeared solid and bumpy or branched (the hepatocyte organoid morphology) while others appeared cystic and spherical (the cholangiocyte or biliary morphology). Over time, the cultures shifted to contain all cholangiocyte morphology organoids in all samples (FIG. 37B). Some individual hepatocyte morphology organoids shifting to cholangiocyte morphology in culture; additionally, the culturing conditions apply a selective pressure in favor of the faster growing cholangiocyte-like organoids. The large, spherical cholangiocyte organoids may break apart during passaging and seed more of these organoids in the new matrigel. The published protocol did not report this cholangiocyte shift phenomenon, which is likely a product of the much older mice used in the study (a few weeks old in the published protocol versus seven to eight months in the experiments here). Bidirectional ability for biliary and hepatic cells to regenerate one another has been reported in vivo, suggesting the possibility of interconverting between these cell types under proper organoid culture conditions (which have yet to be determined). By around two months in culture, the liver organoids began growing much more rapidly, likely due to adaptation to culture conditions and selective pressure for cells able to grow rapidly in vitro. Applicants performed an ATPase growth assay and detected a subtle enhanced growth phenotype in the HFD hepatocyte-derived organoids (CD4 vs HF4 p-value=0.16, CD4 vs HF3 p-value=0.03, ANOVA with multiple testing correction) even after months in culture (FIG. 37C). Additionally, Applicants performed Seq-Well on the liver organoids to determine how faithfully they recapitulate the transcriptional profiles of the hepatocytes from the same animals which were immediately profiled (HF3, HF4, CD4 hepatocyte-enriched samples). Data processing and analysis for this experiment are ongoing.

Follow-Up and Ongoing Experiments

The current pilot dataset analysis has characterized many cell types from multiple compartments, identified biologically meaningful shifts in transcript expression, and nominated pathways which may participate in driving these changes; yet, more work remains to be done to further explore and validate these observations.

In agreement with earlier work from the Yilmaz Lab, the present work observes upregulation of PPAR in HFD intestinal samples. In the data, PPAR upregulation occurred mainly in the proximal region. Applicants also noted significant upregulation of PPAR activity in enterocyte cells from the proximal region, not mentioned in previous work which was focused on stem and progenitor cells. Importantly, the experiments were performed at an earlier time point than in the published work (6 months vs 9-14 months on diet), thus representing earlier initiation of PPAR activation at least in some regions. Additional experiments, such as the organoid, and imaging experiments described in the earlier publication¹, could be performed at the earlier time point used here to validate the findings.

Beyond the gut, Applicants also observe diet-induced changes in the liver. While upregulation of PPAR activity was inconsistent in the liver, it remains a possible driver of liver changes in need of further investigation. In the gut, treatment with a PPAR agonist recapitulated the effects of HFD, and a similar experiment could be performed in the liver or liver organoids to determine whether a PPAR agonist can recapitulate HFD effects in the liver as well. In addition to PPAR, Applicants identified other pathways which may be activated or deactivated in the liver. Modulation of these upstream regulators through agonists or inhibitors will provide insight into the role of these pathways in driving changes in the HFD liver.

In both liver and gut, Applicants noted possible shifts in immune composition, but these shifts are difficult to interpret in existing data due to confounding factors (CD45 sorting in gut samples, technical effects, undersequencing of some samples). Flow analysis to quantify the abundance of immune subsets in the liver and gut will determine whether immune populations, such as B cells in the gut or macrophages in the liver, infiltrate into these organs in HFD. Additionally, Applicants have sequencing data from reference immune sites in the peripheral blood, bone marrow and spleen. Comparing between immune cells within the liver or gut to immune cells outside these organs will reveal how these immune cells respond to the inflammatory or oncogenic environment in the HFD gastrointestinal system. “Spill over” genes from the free RNAs in the media in cell loading complicate comparisons of a given cell type across sample types. Application of a computational tool such as SoupX for background correction to remove this contamination will be needed to properly compare immune cells across organs.

Infiltrating immune cells may travel between the liver and gut and support cross-talk between gastrointestinal and immune sites. Further analysis of bone marrow, peripheral blood and spleen samples may identify immune responses to HFD outside the GI system if such responses exist. In the dataset HFD and CD bone marrow samples do cluster separately, but technical differences in sequencing depth dominate the differences between the HFD and CD data in this compartment. After deeper sequencing, Applicants will be equipped to better compare these samples.

Analysis of sequenced liver organoids is ongoing and when complete will determine how closely the organoids recapitulated the biology of the hepatocytes from the HFD and CD livers. Results may guide further optimization of the organoid culturing protocol. Future organoid experiments will work toward better normalizing seeding efficiency to facilitate comparison of organoid forming efficiency between diets. Ideally, Applicants will be able to grow organoids with a consistent hepatocyte phenotype and controlled seeding from HFD and CD samples. Withdrawal of some growth factors, such as WNTs, from organoid culture during the first few days could select for cells already primed for growth or proliferation in the in vivo environment and may confer a stronger growth advantage to the HFD-derived organoids. If so, this would demonstrate the enhanced ability of HFD hepatocytes to survive and grow in vitro and possibly form tumors in vivo. In the published work with gut organoids from HFD and CD, culturing CD-derived organoids with lipids recapitulated the effects of HFD. Similarly, culturing CD hepatic organoids with these lipids will determine whether these fats also affect these liver organoids in analogous ways.

Extensions of this work to future projects may include building a dataset over a full-time course of 3, 6, 9 and 12 months, repeating experiments with female mice to explore sex-differences in HFD responses, and extending the work to human samples are discussed in detail in Chapter 6. The work described here and these extensions will deepen the understanding of the effects of obesity and diet on the gastrointestinal system and development of diet-induced cancer, and point toward potential therapeutic targets. Further validation and development of these candidate targets may one day lead to improved treatment options for NASH, HCC, and intestinal cancers.

Methods Mice

Mice were maintained on a high fat diet (HFD) or control diet (CD) for 6 months, as described previously. Liver samples (hepatocyte-enriched and NPC-enriched) were obtained as described in Example 3. Intestinal samples (proximal small intestine, distal small intestine and colon) were processed to enrich for crypts, then dissociated to single cell suspensions. Single-cell suspensions were sorted on a Sony SH800 flow sorter into CD45+ (immune) and Epcam+ to increase input of immune cells. One array was loaded for each intestinal sample with a sorted population of 5,000 immune cells and 20,000 Epcam+ cells. Counting of sorted populations showed that only about half as many cell as expected are in the sorted populations, so the arrays were loaded with close to the target of 15,000 cells.

Library Preparation and Sequencing

Samples were run according to the Seq-Well version 2 protocol with second strand synthesis with the following adjustments: increased loading from 10,000 to 15,000 cells, media for loading and sealing was changed from RPMI to Hepatocyte media for liver samples and crypt media for gut, cell loading time was increased from 5 minutes to 15-20 minutes for liver samples and 10 minutes for all other samples. Applicants note that prompt processing of all samples, especially liver samples, is essential to obtain quality so each sample was processed as soon as it was ready, rather than waiting for several samples to run in parallel.

Libraries were sequenced on a Nova-Seq (Illumina) at 12 libraries per run. Undersequenced libraries from experiment 2 were sequenced again to improve sequencing depth. Resequencing of some samples in Experiments 3 and 4 to increase sequencing depth is still needed. Average nGene <1000 may indicate undersequencing. Sequencing output was aligned to mm10 by STAR aligner. Events with fewer than 500 transcripts captured were discarded as non-cells. Remaining cells were filtered on >200 genes expressed. More stringent filtering results in excessive loss of HFD hepatocytes. This filtering does allow some low-quality cells/events into the dataset, but these cells readily cluster together and are filtered out from subsequent analysis.

Sequencing Data Analysis

Filtered data was analyzed using primarily the R package Seurat version 2 from the Satij a Lab. Applicants performed dimensional reduction by Principal Components Analysis (PCA) over the dataset. Applicants selected significant PCs from the Elbow Plot and performed t-Stochastic Neighbor Embedding (tsne) over the selected PCs and Shared Nearest Neighbor (SNN) clustering over those same PCs. Differential expression was performed using the “FindMarkers” function and the Wilcoxon statistical test.

Cell type signatures were created using the AddModuleScore function in Seurat and a list of marker genes for each expected cell type. These module scores were used to assign cell types to SNN clusters. Marker genes for cell types were obtained from Haber et. al. for intestinal cell types and Halpern et.al. for liver cell types. Module scores were also created for selected pathway gene lists, such as KEGG_PPAR in the same way.

To gain further resolution in the analysis, Applicants performed iterative clustering. In very large datasets cell types or subtypes which are small in number compared to the total often do not drive enough of the total variation to clearly cluster out by SNN. By subsetting the data to include only a smaller selection of cells, Applicants increased resolution to call more subtle differences or identify rarer cell types within this subset group as variation driven by the small group of cells is now enough of the total to separate clearly by SNN. Applicants performed iterative clustering over groups selected by sample of origin, and cell type and cluster(s).

Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) from Qiagen on selected differentially expressed gene lists to identify biological processes which may vary between the compared groups. DEGs were identified as described above, and filtered to include only genes with a p-adjusted value of <0.1 and an average log-fold change of >0.25 for input to IPA. Core analysis was run using default settings. Interesting IPA results were curated manually.

Organoid Culture

Hepatocyte organoid culturing was performed as described previously. For organoid Seq-Well experiment, organoids were dissociated to single cell suspension and loaded 15,000 cell per array. On array each was run for organoids from HF3, HF4 and CD4. ATPase growth assay was performed after approximately 2 months in culture. Aspirate media from well, add 65 uL CTG3D (Promega) to each well, seal plate and shake at room temperature 30 minutes. Transfer 15ul to white 384 wp (in triplicate), read at 1 sec lum interval time on luminescence plate reader.

Statistics

Effect size for expression of module scores was calculated Cohen's d. Significance in the organoid growth assay was calculated using ANOVA with correction for multiple testing.

The following references relate to example 4:

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Various modifications and variations of the described methods, pharmaceutical compositions, and kits of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific embodiments, it will be understood that it is capable of further modifications and that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the art are intended to be within the scope of the invention. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure come within known customary practice within the art to which the invention pertains and may be applied to the essential features herein before set forth. 

What is claimed is:
 1. A method of treating liver injury comprising stimulating functional compensation in liver cells by administering an agent that stimulates macrophage Wnt signaling.
 2. The method of claim 1, wherein administering an agent comprises delivering a vector that targets liver macrophages.
 3. The method of claim 1, wherein administering an agent comprises delivery of an agent targeting hepatocytes thereby stimulating macrophage Wnt signaling at the site of livery injury.
 4. A method of decreasing cancer susceptibility and/or inflammation comprising administering a subject in need thereof an inhibitor of peroxisome proliferator-activated receptors (PPARs).
 5. The method of claim 2, wherein the PPAR is alpha, beta/delta or gamma.
 6. The method of claim 2, wherein administration of the inhibitor is localized to the gut or localized to the liver.
 7. The method of claim 2, wherein the subject is obese or on a high fat diet.
 8. A method of reducing risk of proliferation disorders or cancer in the liver comprising administering to a subject in need thereof an agent that increases expression of Sox9 or decreases expression of Lrg5 and Axin
 2. 9. A method of treating an injury in an organ or tissue, comprising: administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes or gene products that have functions in: regulation of proteolysis, chemical homeostasis, secretion by cells, regulation of hydrolase activity, regulation of body fluid levels, homeostatic process, wound healing, glycerolipid metabolic process, response to external stimuli, response to oxygen containing compounds, response to lipid, neutral lipid metabolic process, negative regulation of hydrolase activity, ion homeostasis, response to biotic stimulus, exocytosis, platelet degranulation, response to alcohol, regulated exocytosis, negative regulation of peptidase activity, extracellular matrix, secretory granule, platelet alpha granule, secretory granule lumen, secretory vesicle, vesicle lumen, blood microparticle, intracellular vesicle, extracellular space, cytoplasmic vesicle part, protein lipid complex, enzyme inhibitor activity, enzyme regulator activity, response to hypoxia, apoptosis, complement components functions and activities, or a combination thereof.
 10. The method of claim 1, further comprising: administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in PPAR signaling pathway, complement and/or coagulation cascades, PPARa activated gene expression, biological oxidations, metabolism of lipids and lipoproteins, nasopharyngeal carcinoma, intestine probiotics, plasma cell vs plasmablast, liver cancer, liver specific genes, multiple myeloma, response to UVb radiation, heart atrium vs ventricle, aging kidney no blood, endocrine therapy resistance, liver cancer, breast cancer basal, foxa2 targets, stem cell, lung cancer kras, tlx targets, liver cancer subclass g123, liver cancer subclass proliferation, liver cancer stem cell, liver cancer recurrence, liver cancer subclass s3, hepatoblastoma, liver development, liver hnf1a targets, matrisome, liver cancer krt19, fatty acid catabolic process, ammonium ion metabolic process, protein activation cascade, regulation of wound healing, response to estradiol, response to acid chemical, sterol homeostasis, lipoprotein metabolic process, fatty acid beta oxidation, protein maturation, regulation of locomotion, organic hydroxy compound metabolic process, organic acid biosynthetic process, monocarboxylic acid metabolic process, response to inorganic substance, regulation of vesicle mediated transport, regulation of fatty acid metabolic process, organic hydroxy compound transport, defense response, organophosphate ester transport, lipid homeostasis, secretion, anion transport, regulation of lipid biosynthetic process, response to xenobiotic stimulus, regulation of response to external stimulus, small molecule biosynthetic process, regulation of response to external stimulus, regulation of lipid metabolic process, amine metabolic process, autophagy, regulation of secretion, apoptotic signaling pathway, acute inflammatory response, regulation of catabolic process, maintenance of location, regulation of protein secretion, organic acid metabolic process, response to oxygen levels, regulation of cellular ketone metabolic process, organic acid catabolic process, regulation of response to wounding, regulation of extrinsic apoptotic signaling pathway, cellular lipid catabolic process, regulation of reactive oxygen species metabolic process, detoxification, regulation of peptidase activity, organic anion transport, inflammatory response, negative regulation of cell death, fatty acid metabolic process, lipid metabolic process, divalent inorganic cation homeostasis, regulation of endocytosis, alcohol metabolic process, immune response, cellular lipid metabolic process, monocarboxylic acid transport, negative regulation of apoptotic signaling pathway, multicellular organismal homeostasis, organic hydroxy compound biosynthetic process, regulation of cell death, lipid catabolic process, regulation of lipid metabolic process, regulation of steroid metabolic process, regulation of inflammatory response, response to toxic substance, cellular chemical homeostasis, regulation of transport, regulation of lipid catabolic process, regulation of immune effector process, lipid localization, regulation of proteolysis, regulation of secretion, regulation of response to wounding, regulation of multicellular organismal process, cellular homeostasis, single organism catabolic process, response to oxidative stress, behavior, acute phase response, regulation of response to external stimulus, regulation of apoptotic signaling pathway, regulation of cell proliferation, response to reactive oxygen species, endocytic vesicle, endoplasmic reticulum part, endoplasmic reticulum lumen, endoplasmic reticulum, lipid transporter activity, sulfur compound binding, steroid binding, glycosaminoglycan binding, alcohol binding, carboxylic ester hydrolase activity, lipid binding, receptor binding, coenzyme binding, adipogenesis, xenobiotic metabolism, fatty acid metabolism, coagulation, bile acid metabolism, peroxisome, or a combination thereof.
 3. The method of claim 1, further comprising administering to the subject in need thereof another agent that modulates expression and/or activity of one or more genes or gene products that have functions in HDAC3 targets, photodynamic therapy stress, CEBP targets, tolerant macrophage, response to salirasib, adult tissue stem module, klfl targets, anatomical structure formation involved in morphogenesis, circulatory system process, cellular response to external stimulus, response to wounding, cellular response to extracellular stimulus, cell activation, cellular response to oxygen containing compound, vesicle mediated transport, enzyme linked receptor protein signaling pathway, response to bacterium, regulation of catabolic process, response to ketone, regulation of cell adhesion, response to hormone, blood vessel morphogenesis, response to estrogen, response to radiation, response to extracellular stimulus, cellular response to nitrogen compound, regulation of catalytic activity, vasculature development, response to abiotic stimulus, response to drug, response to growth factor, regulation of protein metabolic process, transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to peptide, hexose metabolic process, cellular response to stress, endocytosis, circulatory system development, response to starvation, hemostasis, response to molecule of bacterial origin, cell surface, peptidase regulator activity, molecular function regulator, peptidase inhibitor activity, phospholipid binding, TNF-a signaling via NFkB, or a combination thereof.
 4. The method of claim 1, wherein the agent modulates expression and/or activity of one or more genes or gene products in Wnt pathway.
 5. The method of claim 1, wherein the agent modulates expression and/or activity of one or more genes or gene products that are markers of hepatic stem cells.
 6. The method of claim 1, wherein the expression and/or activity of the one or more genes or gene products is altered both in response to a zone-dependent injury and a zone-independent injury.
 7. The method of claim 1, wherein the one or more genes or gene products comprises Gclc, Txnrd1, Lars2, Cyp4a14, Apoc2, Apoc1, Cyp2c29, Mt1, Mt2, Saa1, Saa2, Fgl1, Mup17, Mup18, Mup11, Gm23935, mmu-mir-6236, Ly6e, Rnase4, Saa4, Fgl1, Hp, Hpx, Lcn2, Orm1, Apcs, Orm2, Saa1, Saa2, Saa3, Sds, Tacc2, Igfbp1, Cxc11, Thrsp, Serpina3n, Lpin1, Steap4, Mt1, Mt2, Aldh3a2, Cyp2c37, Cyp2c29, Cyp8b1, Ces1d, Apoc1, Hsd17b13, Atp5h, Apoc2, Retsat, Mat1a, Angptl3, Chchd10, Hmgcs2, Cyp4a10, Cyp4a14, Gm26917, Lars2, Hyou1, Arrdc3, Mup12, Gm15564, Pdia3, Gm26924, Sephs2, Grip2, Krt8, Krt18, Plin2, Chka, Gclc, Srxn1, Hmox1, S100a8, S100a9, Mup15, Mup4, Ankrd55, Mup11, Mup5, Mup18, Mup9, Mup6, Mup17, Mup19, Alb, Pck1, Slc2a2, F2, Cyp2e1, Glu1, Arg1, Cdh1, Gls2, Ppargc1a, Sox9, Tbx3, Lgr5, Axin2, or a combination thereof.
 8. The method of claim 1, wherein the one or more genes or gene products are selected from the genes or gene products in any one of Tables 1a-8c or in all of Tables 1a-8c.
 9. The method of claim 1, wherein the agent induces regeneration and/or functional compensation of the organ or tissue.
 10. The method of claim 1, wherein the agent induces generation of cells that compensate for function loss caused by the injury in the organ or tissue.
 11. The method of claim 1, wherein the agent induces cell proliferation in the organ or tissue.
 12. The method of claim 1, wherein the organ or tissue is liver, spleen, intestine, colon, bone marrow, an immune tissue or organ, or a tissue or organ of the gastrointestinal tract.
 13. The method of claim 1, wherein the injury is an acute injury.
 14. The method of claim 1, wherein the injury is a chronic injury.
 15. The method of claim 1, wherein the injury is caused by a metabolic or toxic insult.
 16. The method of claim 1, wherein the injury is caused by high fat diet.
 17. The method of claim 1, wherein the injury is caused by a disease.
 18. The method of claim 1, wherein the injury is caused by a chronic disease.
 19. The method of claim 1, wherein the disease is a liver disease.
 20. The method of claim 19, wherein the liver disease is non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or cirrhosis.
 21. The method of claim 1, wherein the injury is a zone-independent injury.
 22. The method of claim 1, wherein the injury is a zone-dependent injury.
 23. The method of claim 1, wherein the agent is a CRISPR-Cas agent.
 24. A method of treating an injury in an organ or tissue, comprising: a. determining expression of one or more genes from single cells in the organ or tissue at a first time point and a second time point; b. selecting a first subset of genes from the one or more genes, wherein expression of the first subset of genes at the first and the second time points are different; c. determining spatial locations of cells expressing the first subset of genes in the organ or tissue at the first and the second time points by an in situ hybridization assay; d. selecting a second subset of genes based on the spatial locations of the cells expressing the second subset of genes; and e. administering an agent that modulates expression and/or activity of one or more of the second subset of genes to a subject in need thereof. 